Updated on 2024/10/03

写真a

 
Shingo Maeda
 
Organization
Research Field in Medicine and Health Sciences, Medical and Dental Sciences Area Graduate School of Medical and Dental Sciences Contribution Course Department of Bone and Joint Medicine Professor
Title
Professor

Degree

  • Doctor (Medicine) ( 2001.3   Kagoshima University )

Research Interests

  • TGF-beta

  • TGF-beta

  • BMP

  • osteoblast/chondrocyte differentiation

  • 骨芽細胞分化

  • 軟骨細胞分化

  • TGF-β

  • osteoblast differentiation

  • BMP

Research Areas

  • Life Science / Orthopedics

  • Life Science / Orthopedics

  • Life Science / Molecular biology

Education

  • Kagoshima University

    - 2001.3

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    Country: Japan

  • Nagasaki University

    - 1994.3

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    Country: Japan

Research History

  • Kagoshima University   Research Field in Medicine and Health Sciences, Medical and Dental Sciences Area Graduate School of Medical and Dental Sciences Contribution Course Department of Bone and Joint Medicine   Associate Professor

    2020.4

  • 鹿児島大学大学院医歯学総合研究科   骨関節医学   特任准教授

    2020

  • 鹿児島大学大学院医歯学総合研究科   医療関節材料開発講座   特任准教授

    2009.4

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    Country:Japan

  • Kagoshima University   Research Field in Medicine and Health Sciences, Medical and Dental Sciences Area Graduate School of Medical and Dental Sciences Contribution Course Medical Joint Materials(KYOCERA Medical)   Associate Professor

    2009.4 - 2020.3

  • 鹿児島大学大学院医歯学総合研究科   医療関節材料開発講座   特任准教授

    2009 - 2020

  • 財団法人癌研究会癌研究所   生化学部   研究員

    2002.4 - 2009.3

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    Country:Japan

  • 東京大学医科学研究所   ゲノム情報応用診断   研究生

    2000.5 - 2002.3

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    Country:Japan

  • 鹿児島大学医学部附属病院   整形外科   職員(医療系)

    1999.7 - 2000.4

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    Country:Japan

  • 群馬大学生体調節研究所   遺伝情報分野   研究生

    1998.1 - 1999.6

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    Country:Japan

  • Institute of Human Genetics (Jean-Marc Lalouel Lab.), University of Utah, U.S.A.

    1997.4 - 1997.12

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    Country:Japan

  • 鹿児島大学医学部附属病院   整形外科   職員(医療系)

    1995.7 - 1997.3

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    Country:Japan

  • 医療法人社団誠療会成尾整形外科病院   職員(医療系)

    1995.1 - 1995.6

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    Country:Japan

  • 鹿児島大学医学部附属病院   整形外科   職員(医療系)

    1994.5 - 1994.12

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    Country:Japan

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Professional Memberships

  • 日本骨代謝学会

  • 日本軟骨代謝学会

  • 日本整形外科学会

  • Orthopaedic Research Society

Committee Memberships

  • 日本軟骨代謝学会   評議員  

       

Studying abroad experiences

  • 1997.4 - 1997.12   Institute of Human Genetics (Jean-Marc Lalouel Lab.), University of Utah, U.S.A.   Staff

 

Papers

  • Nakano N, Tashiro E, Shimada T, Ebisawa M, Kojima S, Ayabe K, Yamamoto Y, Maeda S, Itoh F, Itoh S .  Involvement of mitogen- and stress-activated protein kinase (MSK)1 in BMP-6-induced chondrocyte differentiation. .  The Journal of biological chemistry   107806   2024.9Involvement of mitogen- and stress-activated protein kinase (MSK)1 in BMP-6-induced chondrocyte differentiation.

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    DOI: 10.1016/j.jbc.2024.107806

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  • Tawaratsumida H, Iuchi T, Masuda Y, Ide T, Maesako S, Miyazaki T, Ijuin T, Maeda S, Taniguchi N .  Zoledronate alleviates subchondral bone collapse and articular cartilage degeneration in a rat model of rotator cuff tear arthropathy. .  Osteoarthritis and cartilage   2024.8

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    Language:English   Publisher:Osteoarthritis and Cartilage  

    Objective: To evaluate the humeral head bone volume of patients with cuff tear arthropathy (CTA) and examine the therapeutic effect of zoledronate in a rat modified model of CTA (mCTA). Design: The bone mass in patients with CTA was measured using Hounsfield units from CT images. The mCTA was induced by transecting the rotator cuff, biceps brachii tendon, and superior half of the joint capsule in adult rat shoulders. A single subcutaneous injection of zoledronate was followed by bone histomorphometry and immunohistochemistry of the humeral head, as well as the Murine Shoulder Arthritis Score (MSAS) assessment. Results: The humeral head bone volume was decreased in patients with CTA. In the mCTA model, M1 macrophages were increased in the synovium and were decreased by zoledronate treatment. The increased expressions of TNF-α, IL-1β and IL-6 in mCTA synovium and articular cartilage were suppressed in the zoledronate-treated mCTA group. The expression of catabolic enzymes in the articular cartilage and MSAS showed similar results. The zoledronate-treated mCTA group showed a decreased subchondral bone collapse with a decreased RANKL/OPG expression ratio and a suppressed number of osteoclasts compared with the control mCTA group. The enhanced expressions of HMGB1 and S100A9 in the mCTA shoulders were eliminated in the zoledronate-treated mCTA group. Conclusions: The humeral head subchondral bone was decreased in patients with CTA. In the mCTA model, the collapse and osteoarthritic changes were prevented by zoledronate administration. Zoledronate seemed to suppress the number of M1 macrophages in the synovium and osteoclasts in the subchondral bone.

    DOI: 10.1016/j.joca.2024.08.005

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  • Tokumoto H, Tominaga H, Maeda S, Sasaki H, Kawamura I, Setoguchi T, Taniguchi N .  Risk factors for vertebral fracture in rheumatoid arthritis patients using biological disease-modifying anti-rheumatic drugs (cases over 5 years): An observational study. .  Medicine103 ( 27 ) e38740   2024.7

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    Language:English   Publisher:Medicine (United States)  

    While biological disease-modifying anti-rheumatic drugs (bDMARDs) are considered beneficial for preventing osteoporosis and bone fracture, it is unclear whether bone loss is involved in the development of vertebral fracture, and few reports have examined the factors related to vertebral fracture in rheumatoid arthritis (RA) patients using bDMARDs. This study aims to identify factors influencing vertebral fracture in RA patients treated with bDMARDs. We retrospectively examined the records of 129 RA patients treated with bDMARDs for over 5 years. The lumbar spine and femoral bone mineral density, Disease Activity Score-28-C-Reactive Protein (DAS28-CRP) value, Simplified Disease Activity Index (SDAI), and modified Health Assessment Questionnaire (mHAQ) score were evaluated. The frequency of new vertebral fracture during the study and their risk factors were investigated. A comparison between the fracture group and the nonfracture group was performed. Multivariate analysis was performed using logistic regression analysis to detect risk factors for new vertebral fracture. The number of patients with new vertebral fracture during follow-up was 15 (11.6%) of the 129 patients in the study. Age and mHAQ score were significantly higher and lumbar spine and femoral neck bone mineral density were significantly lower in the fracture group than the nonfracture group. The risk factors for new vertebral fracture during the disease course were older age and higher mHAQ score indicating no remission over the 5 years of follow-up. In this study, there was no significant difference in disease indices such as the DAS28-CRP value and the SDAI between the fracture and nonfracture groups, suggesting an effective control of RA with bDMARDs. However, age and the mHAQ score, an index of RA dysfunction, were significantly higher in the fracture group. These results suggest that improving functional impairment may be important to prevent vertebral fracture in patients using bDMARDs.

    DOI: 10.1097/MD.0000000000038740

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  • Tominaga H, Tokumoto H, Maeda S, Kawamura I, Sanada M, Kawazoe K, Taketomi E, Taniguchi N .  High prevalence of lumbar spinal stenosis in cases of idiopathic normal-pressure hydrocephalus affects improvements in gait disturbance after shunt operation. .  World neurosurgery: X20   100236   2023.10

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    Language:English   Publisher:World Neurosurgery: X  

    Objective: Idiopathic normal-pressure hydrocephalus (iNPH) is characterized by symptoms of dementia, urinary incontinence, and gait disturbance; however, gait disturbance tends to persist after shunt surgery. Gait disturbance and urinary dysfunction are also major symptoms of lumbar spinal stenosis (LSS). Currently, the epidemiology of the complications of LSS in iNPH is unclear. Here, we evaluated the coexistence rate of LSS in iNPH cases. Methods: This was a retrospective case–control study. Between 2011 and 2017, 224 patients with a median age of 78 years, including 119 males, were diagnosed with iNPH and underwent lumboperitoneal shunts or ventriculoperitoneal shunts. LSS was diagnosed with magnetic resonance imaging by two spine surgeons. Age, sex, body mass index (BMI), Timed Up and Go (TUG) test, Mini Mental State Examination (MMSE) score, and urinary dysfunction were examined. We compared the changes in these variables in the group of patients with iNPH without LSS versus those with both iNPH and LSS. Results: Seventy-three iNPH patients (32.6%) with LSS had significantly higher age and BMI. The existence of LSS did not alter the postoperative improvement rates of MMSE and urinary dysfunction; however, TUG improvement was significantly impaired in the LSS-positive group. Conclusions: LSS affects improvements in gait disturbance of iNPH patients after shunt operation. Because our results revealed that one-third of iNPH patients were associated with LSS, gait disturbance observed in iNPH patients should be considered a potential complication of LSS.

    DOI: 10.1016/j.wnsx.2023.100236

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  • Ijuin T, Iuchi T, Tawaratsumida H, Masuda Y, Tokushige A, Maeda S, Taniguchi N .  Development of a novel animal model of rotator cuff tear arthropathy replicating clinical features of progressive osteoarthritis with subchondral bone collapse. .  Osteoarthritis and cartilage open5 ( 3 ) 100389   2023.9

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    Language:English   Publisher:Osteoarthritis and Cartilage Open  

    Objective: To establish an animal model of modified cuff tear arthropathy (mCTA) in order to better replicate the pathophysiology associated with rotator cuff tear-induced humeral head collapse. Design: mCTA was induced by transection of the rotator cuff, the long head of the biceps brachii (LHB), and superior half of the joint capsule in the right shoulder of 12-week-old rats; the left shoulder underwent sham surgery. The severity of CTA was quantitated using the Murine Shoulder Arthritis Score (MSAS). The trabecular bone of the humeral head and metaphysis was analyzed using bone histomorphometry. The expression of proinflammatory cytokines and catabolic enzymes was evaluated immunohistochemically. Results: In the mCTA model, the MSAS increased starting from 2 weeks after induction, and there was notable subchondral bone collapse with fibrous cells at 4 weeks. The mCTA cartilage exhibited positive staining for TNF-α, IL-1β/6, MMP-3/13, and ADAMTS5. The trabecular bone volume was reduced not only in the subchondral bone but also in the metaphysis of the humeri, and bone resorption was enhanced in these areas. In the collapsed subchondral bone, both bone formation and resorption were increased. The fibrous cells showed expression of TNF-α, IL-6, and MMP-13, along with specific markers of mesenchymal stem cells. Furthermore, the fibrous cells showed osteoblastic characteristics (RUNX2-positive) and expressed RANKL. Conclusions: The LHB and the capsuloligamentous complex are critical stabilizers of the glenohumeral joint, serving to prevent the advancement of CTA following massive rotator cuff tears. Fibrous cells appear to play a role in the humeral head bone resorption.

    DOI: 10.1016/j.ocarto.2023.100389

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  • Koike Y, Takahata M, Nakajima M, Otomo N, Suetsugu H, Liu X, Endo T, Imagama S, Kobayashi K, Kaito T, Kato S, Kawaguchi Y, Kanayama M, Sakai H, Tsuji T, Miyamoto T, Inose H, Yoshii T, Kashii M, Nakashima H, Ando K, Taniguchi Y, Takeuchi K, Ito S, Tomizuka K, Hikino K, Iwasaki Y, Kamatani Y, Maeda S, Nakajima H, Mori K, Seichi A, Fujibayashi S, Kanchiku T, Watanabe K, Tanaka T, Kida K, Kobayashi S, Takahashi M, Yamada K, Takuwa H, Lu HF, Niida S, Ozaki K, Momozawa Y, Genetic Study Group of Investigation Committee on Ossification of the Spinal Ligaments, Yamazaki M, Okawa A, Matsumoto M, Iwasaki N, Terao C, Ikegawa S .  Genetic insights into ossification of the posterior longitudinal ligament of the spine. .  eLife12   2023.7

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    Ossification of the posterior longitudinal ligament of the spine (OPLL) is an intractable disease leading to severe neurological deficits. Its etiology and pathogenesis are primarily unknown. The relationship between OPLL and comorbidities, especially type 2 diabetes (T2D) and high body mass index (BMI), has been the focus of attention; however, no trait has been proven to have a causal relationship. We conducted a meta-analysis of genome-wide association studies (GWASs) using 22,016 Japanese individuals and identified 14 significant loci, 8 of which were previously unreported. We then conducted a gene-based association analysis and a transcriptomewide Mendelian randomization approach and identified three candidate genes for each. Partitioning heritability enrichment analyses observed significant enrichment of the polygenic signals in the active enhancers of the connective/bone cell group, especially H3K27ac in chondrogenic differentiation cells, as well as the immune/hematopoietic cell group. Single-cell RNA sequencing of Achilles tendon cells from a mouse Achilles tendon ossification model confirmed the expression of genes in GWAS and post-GWAS analyses in mesenchymal and immune cells. Genetic correlations with 96 complex traits showed positive correlations with T2D and BMI and a negative correlation with cerebral aneurysm. Mendelian randomization analysis demonstrated a significant causal effect of increased BMI and high bone mineral density on OPLL. We evaluated the clinical images in detail and classified OPLL into cervical, thoracic, and the other types. GWAS subanalyses identified subtype-specific signals. A polygenic risk score for BMI demonstrated that the effect of BMI was particularly strong in thoracic OPLL. Our study provides genetic insight into the etiology and pathogenesis of OPLL and is expected to serve as a basis for future treatment development.

    DOI: 10.7554/eLife.86514

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  • Naohiro Tachibana, Ryota Chijimatsu, Hiroyuki Okada, Takeshi Oichi, Yuki Taniguchi, Yuji Maenohara, Junya Miyahara, Hisatoshi Ishikura, Yasuhide Iwanaga, Yusuke Arino, Kosei Nagata, Hideki Nakamoto, So Kato, Toru Doi, Yoshitaka Matsubayashi, Yasushi Oshima, Asuka Terashima, Yasunori Omata, Fumiko Yano, Shingo Maeda, Shiro Ikegawa, Masahide Seki, Yutaka Suzuki, Sakae Tanaka, Taku Saito .  RSPO2 defines a distinct undifferentiated progenitor in the tendon/ligament and suppresses ectopic ossification. .  Science advances8 ( 33 ) eabn2138   2022.8International journal

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    Ectopic endochondral ossification in the tendon/ligament is caused by repetitive mechanical overload or inflammation. Tendon stem/progenitor cells (TSPCs) contribute to tissue repair, and some express lubricin [proteoglycan 4 (PRG4)]. However, the mechanisms of ectopic ossification and association of TSPCs are not yet known. Here, we investigated the characteristics of Prg4-positive (+) cells and identified that R-spondin 2 (RSPO2), a WNT activator, is specifically expressed in a distinct Prg4+ TSPC cluster. The Rspo2+ cluster was characterized as mostly undifferentiated, and RSPO2 overexpression suppressed ectopic ossification in a mouse Achilles tendon puncture model via chondrogenic differentiation suppression. RSPO2 expression levels in patients with ossification of the posterior longitudinal ligament were lower than those in spondylosis patients, and RSPO2 protein suppressed chondrogenic differentiation of human ligament cells. RSPO2 was induced by inflammatory stimulation and mechanical loading via nuclear factor κB. Rspo2+ cells may contribute to tendon/ligament homeostasis under pathogenic conditions.

    DOI: 10.1126/sciadv.abn2138

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  • 城光寺 豪, 前田 真吾, 大石 一樹, 伊集院 俊郎, 中島 正宏, 俵積田 裕紀, 河村 一郎, 冨永 博之, 武冨 榮二, 池川 志郎, 谷口 昇 .  脊椎後縦靱帯骨化症原因候補遺伝子であるCDC5LはSOX9、COL2A1、WEE1のpre-mRNAスプライシングを調整し初期軟骨細胞分化と細胞増殖を促進する .  日本骨代謝学会学術集会プログラム抄録集39回   136 - 136   2021.10

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  • 城光寺 豪, 前田 真吾, 大石 一樹, 伊集院 俊郎, 中島 正宏, 俵積田 裕紀, 河村 一郎, 冨永 博之, 武冨 榮二, 池川 志郎, 谷口 昇 .  CDC5LはSOX9、COL2A1、Wee1のpre-mRNAスプライシングを調整し初期軟骨細胞分化と増殖を促進する .  日本整形外科学会雑誌95 ( 8 ) S1709 - S1709   2021.8

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  • Go Jokoji, Shingo Maeda, Kazuki Oishi, Toshiro Ijuin, Masahiro Nakajima, Hiroki Tawaratsumida, Ichiro Kawamura, Hiroyuki Tominaga, Eiji Taketomi, Shiro Ikegawa, Noboru Taniguchi .  CDC5L promotes early chondrocyte differentiation and proliferation by modulating pre-mRNA splicing of SOX9, COL2A1, and WEE1. .  The Journal of biological chemistry297 ( 2 ) 100994 - 100994   2021.7Reviewed International journal

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    Ossification of the posterior longitudinal ligament (OPLL) of the spine is a common pathological condition that causes intractable myelopathy and radiculopathy, mainly the result of an endochondral ossification-like process. Our previous genome-wide association study identified six susceptibility loci for OPLL, including the CDC5L gene region. Here, we found CDC5L to be expressed in type II collagen-producing chondrocyte-like fibroblasts in human OPLL specimens, as well as in differentiating ATDC5 chondrocytes. Cdc5l siRNA transfection in murine chondrocytes decreased the expression of the early chondrogenic genes Sox9 and Col2a1, diminished the cartilage matrix production, and enhanced the expression of parathyroid hormone-related protein (a resting chondrocyte marker). We also showed that Cdc5l shRNA suppressed the growth of cultured murine embryonal metatarsal cartilage rudiments, and that Cdc5l knockdown suppressed the growth of ATDC5 cells. Fluorescence-activated cell sorting analysis revealed that the G2/M cell cycle transition was blocked; our data showed that Cdc5l siRNA transfection enhanced expression of Wee1, an inhibitor of the G2/M transition. Cdc5l siRNA also decreased the pre-mRNA splicing efficiency of Sox9 and Col2a1 genes in both ATDC5 cells and primary chondrocytes; conversely, loss of Cdc5l resulted in enhanced splicing of Wee1 pre-mRNA. Finally, an RNA-binding protein immunoprecipitation assay revealed that Cdc5l bound directly to these target gene transcripts. Overall, we conclude that Cdc5l promotes both early chondrogenesis and cartilage growth, and may play a role in the etiology of OPLL, at least in part by fine-tuning the pre-mRNA splicing of chondrogenic genes and Wee1, thus initiating the endochondral ossification process.

    DOI: 10.1016/j.jbc.2021.100994

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  • 城光寺 豪, 前田 真吾, 中島 正宏, 河村 一郎, 八尋 雄平, 冨永 博之, 武冨 榮二, 池川 志郎, 谷口 昇 .  脊柱後縦靱帯骨化症(OPLL)組織にはosteochondral bipotentialな細胞が存在し、GWASによる原因候補遺伝子を発現する .  日本整形外科学会雑誌94 ( 3 ) S689 - S689   2020.3

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  • Yuhei Yahiro, Shingo Maeda, Masato Morikawa, Daizo Koinuma, Go Jokoji, Toshiro Ijuin, Setsuro Komiya, Ryoichiro Kageyama, Kohei Miyazono, Noboru Taniguchi .  BMP-induced Atoh8 attenuates osteoclastogenesis by suppressing Runx2 transcriptional activity and reducing the Rankl/Opg expression ratio in osteoblasts. .  Bone research8 ( 1 ) 32 - 32   2020

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    Adult bone structural integrity is maintained by remodeling via the coupling of osteoclastic bone resorption and osteoblastic bone formation. Osteocytes or osteoblasts express receptor activator of nuclear factor κ-B ligand (Rankl) or osteoprotegerin (Opg) to promote or inhibit osteoclastogenesis, respectively. Bone morphogenetic protein (BMP) is a potent bone inducer, but its major role in adult bone is to induce osteocytes to upregulate sclerostin (Sost) and increase the Rankl/Opg expression ratio, resulting in promotion of osteoclastogenesis. However, the precise effect of BMP-target gene(s) in osteoblasts on the Rankl/Opg expression ratio remains unclear. In the present study, we identified atonal homolog 8 (Atoh8), which is directly upregulated by the BMP-Smad1 axis in osteoblasts. In vivo, Atoh8 was detected in osteoblasts but not osteocytes in adult mice. Although global Atoh8-knockout mice showed only a mild phenotype in the neonate skeleton, the bone volume was decreased and osteoclasts were increased in the adult phase. Atoh8-null marrow stroma cells were more potent than wild-type cells in inducing osteoclastogenesis in marrow cells. Atoh8 loss in osteoblasts increased Runx2 expression and the Rankl/Opg expression ratio, while Runx2 knockdown normalized the Rankl/Opg expression ratio. Moreover, Atoh8 formed a protein complex with Runx2 to inhibit Runx2 transcriptional activity and decrease the Rankl/Opg expression ratio. These results suggest that bone remodeling is regulated elaborately by BMP signaling; while BMP primarily promotes bone resorption, it simultaneously induces Atoh8 to inhibit Runx2 and reduce the Rankl/Opg expression ratio in osteoblasts, suppressing osteoclastogenesis and preventing excessive BMP-mediated bone resorption.

    DOI: 10.1038/s41413-020-00106-0

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  • Costansia Bureta, Takao Setoguchi, Yoshinobu Saitoh, Hiroyuki Tominaga, Shingo Maeda, Satoshi Nagano, Setsuro Komiya, Takuya Yamamoto, Noboru Taniguchi .  TGF-β Promotes the Proliferation of Microglia In Vitro. .  Brain sciences10 ( 1 )   2019.12

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    The activation and proliferation of microglia is characteristic of the early stages of brain pathologies. In this study, we aimed to identify a factor that promotes microglial activation and proliferation and examined the in vitro effects on these processes. We cultured microglial cell lines, EOC 2 and SIM-A9, with various growth factors and evaluated cell proliferation, death, and viability. The results showed that only transforming growth factor beta (TGF-β) caused an increase in the in vitro proliferation of both microglial cell lines. It has been reported that colony-stimulating factor 1 promotes the proliferation of microglia, while TGF-β promotes both proliferation and inhibition of cell death of microglia. However, upon comparing the most effective doses of both (assessed from the proliferation assay), we identified no statistically significant difference between the two factors in terms of cell death; thus, both have a proliferative effect on microglial cells. In addition, a TGF-β receptor 1 inhibitor, galunisertib, caused marked inhibition of proliferation in a dose-dependent manner, indicating that inhibition of TGF-β signalling reduces the proliferation of microglia. Therefore, galunisertib may represent a promising therapeutic agent for the treatment of neurodegenerative diseases via inhibition of nerve injury-induced microglial proliferation, which may result in reduced inflammatory and neuropathic and cancer pain.

    DOI: 10.3390/brainsci10010020

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  • Hiroto Tokumoto, Takao Setoguchi, Yoshinobu Saitoh, Hiromi Sasaki, Satoshi Nagano, Shingo Maeda, Akihide Tanimoto, Noboru Taniguchi .  Neurotensin receptor 1 is a new therapeutic target for human undifferentiated pleomorphic sarcoma growth. .  Molecular carcinogenesis58 ( 12 ) 2230 - 2240   2019.12

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    Undifferentiated pleomorphic sarcoma (UPS) is the second most common soft tissue sarcoma. For patients with unresectable or metastatic disease, chemotherapies are considered, but in many cases they are not curative. There is a need to identify specific molecular dysregulations that can be therapeutic targets. We focused on neurotensin receptor 1 (NTSR1), which belongs to the G-protein-coupled receptor. NTSR1 expression was upregulated in specimens from patients with UPS. Real-time polymerase chain reaction showed that expression of NTSR1 messenger RNA was 5- to 7-fold increased in UPS cells compared with myoblasts. Western blot showed a high expression of NTSR1 protein in UPS cell lines. Knockdown of NTSR1 prevented UPS cell proliferation and invasion. We confirmed that SR48692, an inhibitor of NTSR1, exhibited antitumor activities in UPS cells. The combination index showed that SR48692 and standard chemotherapeutic drugs prevented UPS cell proliferation synergistically. Mouse xenograft models showed that SR48692 inhibited extracellular signal-regulated kinase phosphorylation and enhanced the response to standard chemotherapeutic drugs. Inhibition of NTSR1 improved the effect of standard chemotherapeutic drugs for UPS. SR48692 may be a new drug for targeted UPS therapy.

    DOI: 10.1002/mc.23111

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  • Masato Morikawa, Yoshihide Mitani, Katarina Holmborn, Taichi Kato, Daizo Koinuma, Junko Maruyama, Eleftheria Vasilaki, Hirofumi Sawada, Mai Kobayashi, Takayuki Ozawa, Yasuyuki Morishita, Yasumasa Bessho, Shingo Maeda, Johan Ledin, Hiroyuki Aburatani, Ryoichiro Kageyama, Kazuo Maruyama, Carl-Henrik Heldin, Kohei Miyazono .  The ALK-1/SMAD/ATOH8 axis attenuates hypoxic responses and protects against the development of pulmonary arterial hypertension. .  Science signaling12 ( 607 )   2019.11

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    Dysregulated bone morphogenetic protein (BMP) signaling in endothelial cells (ECs) is implicated in vascular diseases such as pulmonary arterial hypertension (PAH). Here, we showed that the transcription factor ATOH8 was a direct target of SMAD1/5 and was induced in a manner dependent on BMP but independent of Notch, another critical signaling pathway in ECs. In zebrafish and mice, inactivation of Atoh8 did not cause an arteriovenous malformation-like phenotype, which may arise because of dysregulated Notch signaling. In contrast, Atoh8-deficient mice exhibited a phenotype mimicking PAH, which included increased pulmonary arterial pressure and right ventricular hypertrophy. Moreover, ATOH8 expression was decreased in PAH patient lungs. We showed that in cells, ATOH8 interacted with hypoxia-inducible factor 2α (HIF-2α) and decreased its abundance, leading to reduced induction of HIF-2α target genes in response to hypoxia. Together, these findings suggest that the BMP receptor type II/ALK-1/SMAD/ATOH8 axis may attenuate hypoxic responses in ECs in the pulmonary circulation and may help prevent the development of PAH.

    DOI: 10.1126/scisignal.aay4430

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  • Takayuki Nakashima, Satoshi Nagano, Takao Setoguchi, Hiromi Sasaki, Yoshinobu Saitoh, Shingo Maeda, Setsuro Komiya, Noboru Taniguchi .  Tranilast enhances the effect of anticancer agents in osteosarcoma. .  Oncology reports42 ( 1 ) 176 - 188   2019.7

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    Tranilast [N‑(3',4'‑dimethoxycinnamoyl)‑anthranilic acid], initially developed as an antiallergic drug, also exhibits a growth inhibitory effect on various types of cancer. Osteosarcoma is treated mainly with high‑dose methotrexate, doxorubicin, cisplatin and ifosfamide; however, 20‑30% of patients cannot be cured of metastatic disease. We investigated whether tranilast enhances the anticancer effects of chemotherapeutic drugs and analyzed its mechanism of action in osteosarcomas. Tranilast inhibited proliferation of HOS, 143B, U2OS and MG‑63 osteosarcoma cells in a dose‑dependent manner, as well as enhancing the effects of cisplatin and doxorubicin. The average combination index at effect levels for tranilast in combination with cisplatin was 0.57 in HOS, 0.4 in 143B, 0.39 in U2OS and 0.51 in MG‑63 cells. Tranilast and cisplatin synergistically inhibited the viability of osteosarcoma cells. In flow cytometric analysis, although tranilast alone did not induce significant apoptosis, the combination of tranilast and cisplatin induced early and late apoptotic cell death. Expression of cleaved caspase‑3, cleaved poly(ADP‑ribose) polymerase and p‑H2AX was enhanced by tranilast in combination with cisplatin. Tranilast alone increased expression of p21 and Bim protein in a dose‑dependent manner. Cell cycle analysis using flow cytometry demonstrated that the combination of tranilast and cisplatin increased the number of cells in the G2/M phase. Compared with cisplatin alone, the combination increased levels of phospho‑cyclin‑dependent kinase 1 (Y15). In the 143B xenograft model, tumor growth was significantly inhibited by combined tranilast and cisplatin compared with the controls, whereas cisplatin alone did not significantly inhibit tumor growth. In conclusion, tranilast has a cytostatic effect on osteosarcoma cells and enhances the effect of anticancer drugs, especially cisplatin. Enhanced sensitivity to cisplatin was mediated by increased apoptosis through G2/M arrest. Since tranilast has been clinically approved and has few adverse effects, clinical trials of osteosarcoma chemotherapy in combination with tranilast are expected.

    DOI: 10.3892/or.2019.7150

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  • Costansia Bureta, Yoshinobu Saitoh, Hiroto Tokumoto, Hiromi Sasaki, Shingo Maeda, Satoshi Nagano, Setsuro Komiya, Noboru Taniguchi, Takao Setoguchi .  Synergistic effect of arsenic trioxide, vismodegib and temozolomide on glioblastoma. .  Oncology reports41 ( 6 ) 3404 - 3412   2019.6

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    The treatment of glioblastoma is a critical health issue, owing to its resistance to chemotherapy. The current standard of treatment is surgical resection, followed by adjuvant radiotherapy and temozolomide treatment. Long‑term local treatment of glioblastoma is rarely achieved and the majority of the patients undergo relapse. Resistance to temozolomide emerges from numerous signalling pathways that are altered in glioblastoma, including the Hedgehog signalling pathway. Hence, further research is required to identify effective treatment modalities. We investigated the effect of vismodegib, arsenic trioxide and temozolomide on glioblastoma in vitro and in vivo to apply our findings to the clinical setting. WST‑1 assay revealed that glioblastoma proliferation was inhibited following treatment with these drugs either in single or in combination; this synergistic effect was confirmed by CalcuSyn software. Western blot analysis revealed an increase in the expression of cleaved caspase‑3 and γH2AX. Furthermore, there was marked inhibition and decreased tumour growth in mice that received combination therapy, unlike those that received single agent or vehicle treatment. Our results revealed that the combination of arsenic trioxide/vismodegib and temozolomide may be an attractive therapeutic method for the treatment of glioblastoma.

    DOI: 10.3892/or.2019.7100

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  • 城光寺 豪, 前田 真吾, 中島 正宏, 河村 一郎, 八尋 雄平, 冨永 博之, 武冨 榮二, 池川 志郎, 谷口 昇 .  脊柱後縦靱帯骨化症関連遺伝子CDC5Lは骨芽細胞分化を抑制する .  日本整形外科学会雑誌93 ( 3 ) S605 - S605   2019.3

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  • Yoshinobu Saitoh, Costansia Bureta, Hiromi Sasaki, Satoshi Nagano, Shingo Maeda, Tatsuhiko Furukawa, Noboru Taniguchi, Takao Setoguchi .  The histone deacetylase inhibitor LBH589 inhibits undifferentiated pleomorphic sarcoma growth via downregulation of FOS-like antigen 1. .  Molecular carcinogenesis58 ( 2 ) 234 - 246   2019.2

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    Undifferentiated pleomorphic sarcoma (UPS) is the second most frequent soft tissue sarcoma. Because of its resistance to chemotherapy, UPS patients are treated with surgical resection and complementary radiotherapy. However, since standard chemotherapy has not been established, unresectable or metastatic cases result in a poor prognosis. Therefore, the identification of a more effective therapy for UPS patients is needed. The development and progression of malignant tumors involve epigenetic alterations, and histone deacetylases (HDAC) have become a promising chemotherapeutic target. In this study, we investigated the potential effects and mechanisms of an HDAC inhibitor, LBH589, in UPS cells. We confirmed that LBH589 exhibits potent antitumor activities in four human UPS cell lines (GBS-1, TNMY-1, Nara-F, and Nara-H) and IC50 values ranged from 7 to 13 nM. A mouse xenograft model showed that LBH589 treatment effectively suppressed tumor growth. FACS analysis showed that LBH589 induced apoptosis and G2/M cell cycle arrest. Among apoptosis-related proteins, the expressions of Bcl-2 and Bcl-xL were decreased and the expression of Bak and Bim increased. Among cell cycle-related proteins, reductions of CDK1, p-CDK1, cyclin B1, Aurora A, and Aurora B were observed after LBH589 treatment. RNA microarray identified the FOS-like antigen 1 (FOSL1) gene as a downregulated gene in response to LBH589 in UPS cells. While knockdown of FOSL1 decreased UPS cell proliferation, overexpression induced cell proliferation. Our results show that LBH589 could be a promising chemotherapeutic agent in the treatment of UPS and downregulation of the FOSL1 gene could be the new molecular target of UPS treatment.

    DOI: 10.1002/mc.22922

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  • Yahiro Y, Maeda S, Shinohara N, Jokoji G, Sakuma D, Setoguchi T, Ishidou Y, Nagano S, Komiya S, Taniguchi N .  PEG10 counteracts signaling pathways of TGF-β and BMP to regulate growth, motility and invasion of SW1353 chondrosarcoma cells. .  Journal of bone and mineral metabolism37 ( 3 ) 441 - 454   2018.8Reviewed

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)  

    Recently, we reported highly active transforming growth factor (TGF)-β and bone morphogenetic protein (BMP) signaling in human chondrosarcoma samples and concurrent downregulation of paternally expressed gene 10 (PEG10). PEG10 expression was suppressed by TGF-β signaling, and PEG10 interfered with the TGF-β and BMP-SMAD pathways in chondrosarcoma cells. However, the roles of PEG10 in bone tumors, including chondrosarcoma, remain unknown. Here, we report that PEG10 promotes SW1353 chondrosarcoma cell growth by preventing TGF-β1-mediated suppression. In contrast, PEG10 knockdown augments the TGF-β1-induced motility of SW1353 cells. Individually, TGF-β1 and PEG10 siRNA increase AKT phosphorylation, whereas an AKT inhibitor, MK2206, mitigates the effect of PEG10 silencing on cell migration. SW1353 cell invasion was enhanced by BMP-6, which was further increased by PEG10 silencing. The effect of siPEG10 was suppressed by inhibitors of matrix metalloproteinase (MMP). BMP-6 induced expression of MMP-1, -3, and -13, and PEG10 lentivirus or PEG10 siRNA downregulated or further upregulated these MMPs, respectively. PEG10 siRNA increased BMP-6-induced phosphorylation of p38 MAPK and AKT, whereas the p38 inhibitor SB203580 and MK2206 diminished SW1353 cell invasion by PEG10 siRNA. SB203580 and MK2206 impeded the enhancing effect of PEG10 siRNA on the BMP-6-induced expression of MMP-1, -3, and -13. Our findings suggest dual functions for PEG10: accelerating cell growth by suppressing TGF-β signaling and inhibiting cell motility and invasion by interfering with TGF-β and BMP signaling via the AKT and p38 pathways, respectively. Thus, PEG10 might be a molecular target for suppressing the aggressive phenotypes of chondrosarcoma cells.

    DOI: 10.1007/s00774-018-0946-8

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  • Yasuhiro Ishidou, Kanehiro Matsuyama, Daisuke Sakuma, Takao Setoguchi, Satoshi Nagano, Ichiro Kawamura, Shingo Maeda, Setsuro Komiya .  Osteoarthritis of the hip joint in elderly patients is most commonly atrophic, with low parameters of acetabular dysplasia and possible involvement of osteoporosis .  ARCHIVES OF OSTEOPOROSIS12 ( 1 ) 30 - 30   2017.12

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    A Summary As elderly patients with hip osteoarthritis aged, acetabular dysplasia parameters decreased (Sharp's angle, acetabular roof obliquity angle, and acetabular head index) and the incidence of the atrophic type increased. Vertebral body fracture was more frequent in the atrophic type, suggesting the involvement of osteoporosis at the onset of hip osteoarthritis.
    Introduction
    Osteoarthritis (OA) is associated with increased bone formation at a local site. However, excessive bone resorption has also been found to occur in the early stages of OA. Osteoporosis may be involved in the onset of OA in elderly patients. We conducted a cross-sectional radiographic study of patients with hip OA and examined the association between age and factors of acetabular dysplasia (Sharp's angle, acetabular roof obliquity angle, and acetabular head index) as well as the osteoblastic response to determine the potential involvement of osteoporosis.
    Methods
    This study included 366 patients (58 men, 308 women) who had undergone total hip arthroplasty for the diagnosis of hip OA. We measured the parameters of acetabular dysplasia using preoperative frontal X-ray images and evaluated each patient according to Bombelli classification of OA (hypertrophic, normotrophic, or atrophic type).
    Results
    As the patients aged, the parameters of acetabular dysplasia decreased. The incidence of the atrophic type of OA was significantly higher in older patients. Vertebral body fractures were more frequent in the atrophic type than in the other types. Additionally, the index of acetabular dysplasia was lower in the atrophic type. By contrast, the hypertrophic type was present in relatively younger patients and was associated with an increased index of acetabular dysplasia.
    Conclusion
    In elderly patients with hip OA, the parameters of acetabular dysplasia decreased and the incidence of the atrophic type increased as the patients aged. The frequency of vertebral body fracture was high in patients with the atrophic type, suggesting the involvement of osteoporosis in the onset of hip OA.

    DOI: 10.1007/s11657-017-0325-4

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  • Naohiro Shinohara, Shingo Maeda, Yuhei Yahiro, Daisuke Sakuma, Kanehiro Matsuyama, Katsuyuki Imamura, Ichiro Kawamura, Takao Setoguchi, Yasuhiro Ishidou, Satoshi Nagano, Setsuro Komiya .  TGF-beta signalling and PEG10 are mutually exclusive and inhibitory in chondrosarcoma cells .  SCIENTIFIC REPORTS7 ( 1 ) 13494 - 13494   2017.10Reviewed

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    Histological distinction between enchondroma and chondrosarcoma is difficult because of a lack of definitive biomarkers. Here, we found highly active transforming growth factor-beta (TGF-beta) and bone morphogenetic protein (BMP) signalling in human chondrosarcomas compared with enchondromas by immunohistochemistry of phosphorylated SMAD3 and SMAD1/5. In contrast, the chondrogenic master regulator SOX9 was dramatically down-regulated in grade 1 chondrosarcoma. Paternally expressed gene 10 (PEG10) was identified by microarray analysis as a gene overexpressed in chondrosarcoma SW1353 and Hs 819. T cells compared with C28/I2 normal chondrocytes, while TGF-beta 1 treatment, mimicking higher grade tumour conditions, suppressed PEG10 expression. Enchondroma samples exhibited stronger expression of PEG10 compared with chondrosarcomas, suggesting a negative association of PEG10 with malignant cartilage tumours. In chondrosarcoma cell lines, application of the TGF-beta signalling inhibitor, SB431542, increased the protein level of PEG10. Reporter assays revealed that PEG10 repressed TGF-beta and BMP signalling, which are both SMAD pathways, whereas PEG10 knockdown increased the level of phosphorylated SMAD3 and SMAD1/5/9. Our results indicate that mutually exclusive expression of PEG10 and phosphorylated SMADs in combination with differentially expressed SOX9 is an index to distinguish between enchondroma and chondrosarcoma, while PEG10 and TGF-beta signalling are mutually inhibitory in chondrosarcoma cells.

    DOI: 10.1038/s41598-017-13994-w

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  • Kengo Takahashi, Takao Setoguchi, Arisa Tsuru, Yoshinobu Saitoh, Satoshi Nagano, Yasuhiro Ishidou, Shingo Maeda, Tatsuhiko Furukawa, Setsuro Komiya .  Inhibition of casein kinase 2 prevents growth of human osteosarcoma .  ONCOLOGY REPORTS37 ( 2 ) 1141 - 1147   2017.2

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    High-dose chemotherapy and surgical treatment have improved the prognosis of osteosarcoma. However, more than 20% of patients with osteosarcoma still have a poor prognosis. We investigated the expression and function of casein kinase 2 (CK2) in osteosarcoma growth. We then examined the effects of CX-4945, a CK2 inhibitor, on osteosarcoma growth in vitro and in vivo to apply our findings to the clinical setting. We examined the expression of CK2 alpha and CK2 beta by western blot analysis, and performed WST-1 assays using CK2 alpha and CK2 beta siRNA or CX-4945. Flow cytometry and western blot analyses were performed to evaluate apoptotic cell death. Xenograft models were used to examine the effect of CX-4945 in vivo. Western blot analysis revealed upregulation of CK2 alpha and CK2 beta in human osteosarcoma cell lines compared with human osteoblast cells or mesenchymal stem cells. WST assay showed that knockdown of CK2 alpha or CK2 beta by siRNA inhibited the proliferation of human osteosarcoma cells. Treatment with 3 mu M of CX-4945 inhibited osteosarcoma cell proliferation; however, the same concentration of CX-4945 did not affect the proliferation of human mesenchymal stem cells. Additionally, treatment with CX-4945 inhibited the proliferation of human osteosarcoma cells in a dose-dependent manner. Western blot and flow cytometry analyses showed that treatment with CX-4945 promoted apoptotic death of osteosarcoma cells. The xenograft model showed that treatment with CX-4945 significantly prevented osteosarcoma growth in vivo compared with control vehicle treatment. Our findings indicate that CK2 may be an attractive therapeutic target for treating osteosarcoma.

    DOI: 10.3892/or.2016.5310

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  • Yoshinobu Saitoh, Takao Setoguchi, Masahito Nagata, Arisa Tsuru, Shunsuke Nakamura, Satoshi Nagano, Yasuhiro Ishidou, Hiroko Nagao-Kitamoto, Masahiro Yokouchi, Shingo Maeda, Akihide Tanimoto, Tatsuhiko Furukawa, Setsuro Komiya .  Combination of Hedgehog inhibitors and standard anticancer agents synergistically prevent osteosarcoma growth .  International Journal of Oncology48 ( 1 ) 235 - 242   2016.1Combination of Hedgehog inhibitors and standard anticancer agents synergistically prevent osteosarcoma growthReviewed

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    DOI: 10.3892/ijo.2015.3236.

  • Tsuru A, Setoguchi T, Matsunoshita Y, Nagao-Kitamoto H, Nagano S, Yokouchi M, Maeda S, Ishidou Y, Yamamoto T, Komiya S .  Hairy/enhancer-of-split related with YRPW motif protein 1 promotes osteosarcoma metastasis via matrix metallopeptidase 9 expression. .  Br J Cancer112   1232 - 1240   2015.3Hairy/enhancer-of-split related with YRPW motif protein 1 promotes osteosarcoma metastasis via matrix metallopeptidase 9 expression.Reviewed

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  • Nagao-Kitamoto H, Nagata M, Nagano S, Kitamoto S, Ishidou Y, Yamamoto T, Nakamura S, Tsuru A, Abematsu M, Fujimoto Y, Yokouchi M, Kitajima S, Yoshioka T, Maeda S, Yonezawa S, Komiya S, Setoguchi T. .  GLI2 is a novel therapeutic target for metastasis of osteosarcoma .  Int J Cancer136 ( 6 ) 1276 - 1284   2015.3GLI2 is a novel therapeutic target for metastasis of osteosarcomaReviewed

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  • Nagao-Kitamoto H, Setoguchi T, Kitamoto S, Nakamura S, Tsuru A, Nagata M, Nagano S, Ishidou Y, Yokouchi M, Kitajima S, Yoshioka T, Maeda S, Yonezawa S, Komiya S .  Ribosomal protein S3 regulates GLI2-mediated osteosarcoma invasion .  Cancer Lett356   855 - 861   2015.1Ribosomal protein S3 regulates GLI2-mediated osteosarcoma invasionReviewed

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  • Nakajima M, Takahashi A, Tsuji T, 省略, Maeda S (34 人中12 番目), 省略, Ikegawa S. .  A genome-wide association study identifies susceptibility loci for ossification of the posterior longitudinalligament of the spine. .  Nature Genetics46   1012 - 1016   2014.9A genome-wide association study identifies susceptibility loci for ossification of the posterior longitudinalligament of the spine.Reviewed

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  • Imamura K, Maeda S (corresponding), Kawamura I, Matsuyama K, Shinohara N, Yahiro Y, Nagano S, Setoguchi T, Yokouchi M, Ishidou Y, Komiya S. .  Human Immunodeficiency Virus Type I Enhancer Binding Protein 3 is Essential for the Expression of Asparagine-linked Glycosylation 2 in the Regulation of Osteoblast and Chondrocyte Differentiation. .  J Biol Chem289 ( 14 ) 9865 - 9879   2014.4Human Immunodeficiency Virus Type I Enhancer Binding Protein 3 is Essential for the Expression of Asparagine-linked Glycosylation 2 in the Regulation of Osteoblast and Chondrocyte Differentiation. Reviewed

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  • Kakoi H, Maeda S (equally first, corresponding), Shinohara N, Matsuyama K, Imamura K, Kawamura I, Nagano S, Setoguchi T, Yokouchi M, Ishidou Y, Komiya S. .  BMP signaling upregulates neutral sphingomyelinase 2 to suppress chondrocyte maturation via the Akt signaling pathway as a negative feedback mechanism. .  J Biol Chem289 ( 12 ) 8135 - 8150   2014.3BMP signaling upregulates neutral sphingomyelinase 2 to suppress chondrocyte maturation via the Akt signaling pathway as a negative feedback mechanism.Reviewed

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  • Kawamura I, Maeda S (corresponding author), Imamura K, Setoguchi T, Yokouchi M, Ishidou Y, Komiya S. .  SnoN Suppresses Maturation of Chondrocytes by Mediating Signal Cross-talk between Transforming Growth Factor-β and Bone Morphogenetic Protein Pathways. .  J Biol Chem287 ( 34 ) 29101 - 29113   2012.8SnoN Suppresses Maturation of Chondrocytes by Mediating Signal Cross-talk between Transforming Growth Factor-β and Bone Morphogenetic Protein Pathways.Reviewed

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  • Nagao H, Setoguchi T, Kitamoto S, Ishidou Y, Nagano S, Yokouchi M, Abematsu M, Kawabata N, Maeda S, Yonezawa S, Komiya S. .  RBPJ is a novel target for rhabdomyosarcoma therapy. .  PLoS One7 ( 7 ) e39268   2012.7RBPJ is a novel target for rhabdomyosarcoma therapy.Reviewed

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  • Tanabe F, Yone K, Kawabata N, Sakakima H, Matsuda F, Ishidou Y, Maeda S, Abematsu M, Komiya S, Setoguchi T. .  Accumulation of p62 in degenerated spinal cord under chronic mechanical compression: functional analysis of p62 and autophagy in hypoxic neuronal cells. .  Autophagy7 ( 12 ) 1462 - 1471   2011.12Accumulation of p62 in degenerated spinal cord under chronic mechanical compression: functional analysis of p62 and autophagy in hypoxic neuronal cells.Reviewed

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  • Kawabata N, Ijiri K, Ishidou Y, Yamamoto T, Nagao H, Nagano S, Maeda S, Komiya S, Setoguchi T. .  Pharmacological inhibition of the Hedgehog pathway prevents human rhabdomyosarcoma cell growth. .  Int J Oncol39 ( 4 ) 899 - 906   2011.10Pharmacological inhibition of the Hedgehog pathway prevents human rhabdomyosarcoma cell growth.Reviewed

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  • Yuzawa H, Koinuma D, Maeda S, Yamamoto K, Miyazawa K, Imamura T. .  Arkadia represses the expression of myoblast differentiation markers through degradation of Ski and the Ski-bound Smad complex in C2C12 myoblasts. .  Bone44   53 - 60   2009Arkadia represses the expression of myoblast differentiation markers through degradation of Ski and the Ski-bound Smad complex in C2C12 myoblasts.Reviewed

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  • Tominaga H, Maeda S (Corresponding author), Miyoshi H, Miyazono K, Komiya S, Imamura T. .  Expression of Osterix inhibits bone morphogenetic protein-induced chondrogenic differentiation of mesenchymal progenitor cells. .  J Bone Miner Metab27   36 - 45   2009Expression of Osterix inhibits bone morphogenetic protein-induced chondrogenic differentiation of mesenchymal progenitor cells.Reviewed

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  • Hayashi M, Maeda S (Corresponding author), Aburatani H, Kitamura K, Miyoshi H, Miyazono K, Imamura T. .  Pitx2 prevents osteoblastic transdifferentiation of myoblasts by bone morphogenetic proteins. .  J Biol Chem283   565 - 571   2008Pitx2 prevents osteoblastic transdifferentiation of myoblasts by bone morphogenetic proteins.Reviewed

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  • Tominaga H, Maeda S (Corresponding author), Hayashi M, Takeda S, Akira S, Komiya S, Nakamura T, Akiyama H, Imamura T. .  CCAAT/enhancer-binding Protein β Promotes Osteoblast Differentiation by Enhancing Runx2 activity with ATF4. .  Mol Biol Cell19   5373 - 5386   2008CCAAT/enhancer-binding Protein β Promotes Osteoblast Differentiation by Enhancing Runx2 activity with ATF4.Reviewed

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  • Shirakawa K†, Maeda S†(†: equal contribution), Gotoh T, Hayashi M, Shinomiya K, Ehata S, Nishimura R, Mori M, Onozaki K, Hayashi H, Uematsu S, Akira S, Ogata E, Miyazono K, Imamura T. .  CCAAT/enhancer-binding protein homologous protein (CHOP) regulates osteoblast differentiation. .  Mol Cell Biol26   6105 - 6116   2006CCAAT/enhancer-binding protein homologous protein (CHOP) regulates osteoblast differentiation.Reviewed

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  • Maeda S, Hayashi M, Komiya S, Imamura T, Miyazono K. .  Endogenous TGF-β signaling suppresses maturation of osteoblastic mesenchymal cells. .  EMBO J23   552 - 563   2004Endogenous TGF-β signaling suppresses maturation of osteoblastic mesenchymal cells.Reviewed

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  • Maeda S, Nobukuni T, Shimo-Onoda K, Hayashi K, Yone K, Komiya S, Inoue I. .  Sortilin is upregulated during osteoblastic differentiation of mesenchymal stem cells and promotes extracellular matrix mineralization. .  J Cell Physiol193 ( 1 ) 73 - 79   2002.10Sortilin is upregulated during osteoblastic differentiation of mesenchymal stem cells and promotes extracellular matrix mineralization.Reviewed

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  • Furushima K, Shimo-Onoda K, Maeda S, Nobukuni T, Ikari K, Koga H, Komiya S, Nakajima T, Harata S, Inoue I. .  Large-scale screening for candidate genes of ossification of the posterior longitudinal ligament of the spine. .  J Bone Miner Res17 ( 1 ) 128 - 137   2002.1Large-scale screening for candidate genes of ossification of the posterior longitudinal ligament of the spine.Reviewed

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  • Havelka S, Vesela M, Pavelkova A, Ruzickova S, Koga H, Maeda S, Inoue I, Halman L. .  Are DISH and OPLL genetically related? .  Ann Rheum Dis60 ( 9 ) 902 - 903   2001.9Are DISH and OPLL genetically related?Reviewed

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  • Maeda S, Ishidou Y, Koga H, Taketomi E, Ikari K, Komiya S, Takeda J, Sakou T, Inoue I. .  Functional impact of human collagen alpha2(XI) gene polymorphism in pathogenesis of ossification of the posterior longitudinal ligament of the spine. .  J Bone Miner Res16 ( 5 ) 948 - 957   2001.5Functional impact of human collagen alpha2(XI) gene polymorphism in pathogenesis of ossification of the posterior longitudinal ligament of the spine.Reviewed

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  • Ikari K, Onda H, Furushima K, Maeda S, Harata S, Takeda J. .  Establishment of an optimized set of 406 microsatellite markers covering the whole genome for the Japanese population. .  J Hum Genet46 ( 4 ) 207 - 210   2001.4Establishment of an optimized set of 406 microsatellite markers covering the whole genome for the Japanese population.Reviewed

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  • Maeda S, Ishidou Y, Koga H, Taketomi E, Ikari K, Komiya S, Takeda J, Sakou T, Inoue I. .  Functional impact of human collagen alpha 2(XI) gene polymorphism in pathogenesis of ossification of the posterior longitudinal ligament of the spine .  Journal of Bone and Mineral Research16   948 - 957   2001.3Functional impact of human collagen alpha 2(XI) gene polymorphism in pathogenesis of ossification of the posterior longitudinal ligament of the spineReviewed

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    DOI: 10.1359/jbmr.2001.16.5.948

  • Maeda S, Koga H, Matsunaga S, Numasawa T, Ikari K, Furushima K, Harata S, Takeda J, Sakou T, Komiya S, Inoue I. .  Gender-specific haplotype association of collagen alpha2 (XI) gene in ossification of the posterior longitudinal ligament of the spine. .  J Hum Genet46 ( 1 ) 1 - 4   2001.1Gender-specific haplotype association of collagen alpha2 (XI) gene in ossification of the posterior longitudinal ligament of the spine.Reviewed

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  • 前田真吾, 古賀公明, 井ノ上逸朗, 酒匂崇. .  後縦靭帯骨化症候補遺伝子COL11A2の多型によるmRNA発現の差. .  臨床整形外科35   559 - 564   2000.1後縦靭帯骨化症候補遺伝子COL11A2の多型によるmRNA発現の差.Reviewed

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  • 前田真吾 .  脊椎後縦靭帯骨化症(OPLL)の原因候補遺伝子ヒトXI型コラーゲンα2鎖(COL11A2)の1塩基多型(SNP)がもたらす機能変化. .  鹿児島大学医学部医師会報20   135 - 137   2000脊椎後縦靭帯骨化症(OPLL)の原因候補遺伝子ヒトXI型コラーゲンα2鎖(COL11A2)の1塩基多型(SNP)がもたらす機能変化.Reviewed

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  • Numasawa T, Koga H, Ueyama K, Maeda S, Sakou T, Harata S, Leppert M, Inoue I. .  Human retinoic X receptor beta: complete genomic sequence and mutation search for ossification of posterior longitudinal ligament of the spine. .  J Bone Miner Res14 ( 4 ) 500 - 508   1999.4Human retinoic X receptor beta: complete genomic sequence and mutation search for ossification of posterior longitudinal ligament of the spine.Reviewed

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  • 前田真吾, 古賀公明, 井ノ上逸朗, 酒匂崇. .  後縦靭帯骨化症候補遺伝子COL11A2の多型によるmRNA発現の差. .  日本脊椎外科学会雑誌10   146   1999後縦靭帯骨化症候補遺伝子COL11A2の多型によるmRNA発現の差.Reviewed

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  • Hayashi K, Ishidou Y, Yonemori K, Nagamine T, Origuchi N, Maeda S, Imamura T, Kato M, Yoshida H, Sampath TK, ten Dijke P, Sakou T. .  Expression and localization of bone morphogenetic proteins (BMPs) and BMP receptors in ossification of the ligamentum flavum. .  Bone21 ( 1 ) 23 - 30   1997.7Expression and localization of bone morphogenetic proteins (BMPs) and BMP receptors in ossification of the ligamentum flavum.Reviewed

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  • Matsunaga S, Sakou T, Sunahara N, Oonishi T, Maeda S, Nakanisi K. .  Biomechanical analysis of buckling alignment of the cervical spine. Predictive value for subaxial subluxation after occipitocervical fusion. .  Spine (Phila Pa 1976)22 ( 7 ) 765 - 771   1997.4Biomechanical analysis of buckling alignment of the cervical spine. Predictive value for subaxial subluxation after occipitocervical fusion.Reviewed

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  • 和田正一, 酒匂崇, 米和徳, 吉野伸司, 宮内裕史, 石堂康弘, 長嶺智徳, 前田真吾. .  実験的脊髄損傷後の遅発性神経細胞死に対する興奮性アミノ酸の作用. .  日本パラプレジア医学会雑誌10   64 - 65   1997実験的脊髄損傷後の遅発性神経細胞死に対する興奮性アミノ酸の作用.Reviewed

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  • Ijiri K, Matsunaga S, Fukuyama K, Maeda S, Sakou T, Kitano M, Senba I. .  The effect of pulsing electromagnetic field on bone ingrowth into a porous coated implant. .  Anticancer Res16 ( 5A ) 2853 - 2856   1996.9The effect of pulsing electromagnetic field on bone ingrowth into a porous coated implant.Reviewed

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  • Yonemori K, Matsunaga S, Ishidou Y, Maeda S, Yoshida H. .  Early effects of electrical stimulation on osteogenesis. .  Bone19 ( 2 ) 173 - 180   1996.8Early effects of electrical stimulation on osteogenesis.Reviewed

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  • 米和徳, 酒匂崇, 川内義久, 中川雅裕, 西村謙一, 前田真吾. .  経皮的椎間板摘出術における適応の再評価. .  日本脊椎外科学会雑誌7   25   1996経皮的椎間板摘出術における適応の再評価.Reviewed

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Books

  • Smad Transcriptional Co-activators and Co-repressors.

    Kohei Miyazono, Shingo Maeda, Takeshi Imamura( Role: Joint author)

    PROTEINS AND CELL REGULATION VOLUME 5, Smad Signal Transduction: Smads in Proliferation, Differentiation and Disease.P. ten Dijke and C.-H. Heldin (eds.)・Springer  2006 

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  • 先端医療シリーズ8・整形外科 診断と治療の最先端 (編集 杉岡洋一, 編集顧問 越智隆弘・石井清一, 編集 岩本幸英・黒澤尚・中村利考・松野丈夫)

    井ノ上逸朗, 前田真吾, 猪狩勝則( Role: Joint author)

    後縦靭帯骨化症遺伝要因の解明, 先端医療技術研究所発行  2000 

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MISC

  • Rspo2/Prg4-Positive Cells Contribute to Ligament/Tendon Homeostasis Through Suppression of Ectopic Endochondral Ossification

    Naohiro Tachibana, Ryota Chijimatsu, Hiroyuki Okada, Yuki Taniguchi, Takeshi Oichi, Hideki Nakamoto, So Kato, Toru Doi, Yoshitaka Matsubayashi, Yasushi Oshima, Fumiko Yano, Shingo Maeda, Sakae Tanaka, Taku Saito

    JOURNAL OF BONE AND MINERAL RESEARCH   37   1 - 1   2022.2

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    Web of Science

  • 脊椎後縦靭帯骨化症原因候補遺伝子CDC5Lは骨芽細胞分化を抑制し,初期軟骨細胞分化を促進する

    城光寺豪, 城光寺豪, 前田真吾, 中島正宏, 河村一郎, 八尋雄平, 八尋雄平, 冨永博之, 武冨榮二, 池川志郎, 谷口昇, 谷口昇

    日本骨代謝学会学術集会プログラム抄録集(CD-ROM)   38th   2020

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  • 脊椎後縦靱帯骨化症原因候補遺伝子CDC5Lは初期軟骨細胞分化を促進する

    城光寺豪, 城光寺豪, 前田真吾, 中島正宏, 河村一郎, 八尋雄平, 八尋雄平, 冨永博之, 武冨榮二, 池川志郎, 谷口昇, 谷口昇

    日本整形外科学会雑誌   94 ( 8 )   2020

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  • CDC5L, a genetically associated gene of OPLL, inhibits osteogenesis and promotes early chondrogenesis

    城光寺豪, 城光寺豪, 前田真吾, 中島正宏, 河村一郎, 八尋雄平, 冨永博之, 武冨榮二, 池川志郎, 谷口昇, 谷口昇

    日本軟骨代謝学会プログラム・抄録集   33rd   2020

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  • 脊椎後縦靭帯骨化症原因候補遺伝子CDC5Lは骨芽細胞分化を抑制し,初期軟骨細胞分化を促進する

    城光寺豪, 城光寺豪, 前田真吾, 中島正宏, 河村一郎, 八尋雄平, 八尋雄平, 冨永博之, 武冨榮二, 池川志郎, 谷口昇, 谷口昇

    日本整形外科学会雑誌   94 ( 3 )   2020

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  • Functional analysis of a candidate causal gene of ossification of the posterior longitudinal ligament, CDC5L.

    Go Jokoji, Ichiro Kawamura, Yuhei Yahiro, Hiroyuki Tominaga, Noboru Taniguchi, Shingo Maeda, Eiji Taketomi, Shiro Ikegawa, Masahiro Nakajima

    JOURNAL OF BONE AND MINERAL RESEARCH   34   309 - 310   2019.12

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    Web of Science

  • 脊椎後縦靱帯骨化症原因候補遺伝子CDC5Lの機能解析

    城光寺豪, 前田真吾, 中島正宏, 河村一郎, 八尋雄平, 冨永博之, 武冨榮二, 池川志郎, 谷口昇

    日本整形外科学会雑誌   93 ( 8 )   2019

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  • 脊椎後縦靭帯骨化症原因候補遺伝子CDC5Lの軟骨細胞分化における役割

    城光寺豪, 城光寺豪, 前田真吾, 中島正宏, 河村一郎, 八尋雄平, 八尋雄平, 冨永博之, 武冨榮二, 池川志郎, 谷口昇, 谷口昇

    日本軟骨代謝学会プログラム・抄録集   32nd   2019

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  • 脊椎後縦靭帯骨化症原因候補遺伝子CDC5Lの機能解析

    城光寺豪, 城光寺豪, 前田真吾, 冨永博之, 八尋雄平, 河村一郎, 中島正宏, 池川志郎, 谷口昇

    日本骨代謝学会学術集会プログラム抄録集   37th   2019

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  • 整形トピックス 新規骨形成蛋白BMPシグナル標的遺伝子Atoh8による骨芽細胞分化・骨形成制御

    八尋 雄平, 前田 真吾, 小宮 節郎

    整形外科   69 ( 2 )   134 - 134   2018.2

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  • Functional Analysis of a Candidate of Causal Gene for Ossification of the Posterior Longitudinal Ligament of the Spine, CDC5L.

    Shingo Maeda, Masahiro Nakajima, Ichiro Kawamura, Yuhei Yahiro, Hiroyuki Tominaga, Yasuhiro Ishidou, Eiji Taketomi, Shiro Ikegawa, Setsuro Komiya

    JOURNAL OF BONE AND MINERAL RESEARCH   32   S285 - S285   2017.12

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    Web of Science

  • An impact of CCN2-BMP-2 complex upon chondrocyte biology: evoking a signalling pathway bypasses ERK and Smads- Reviewed

    Shingo Maeda

    J Biochem   150 ( 3 )   219 - 221   2011.9

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  • BMP receptor signaling: transcriptional targets, regulation of signals, and signaling cross-talk. Reviewed

    Miyazono K, Maeda S, Imamura T.

    Cytokine Growth Factor Rev   16   251 - 263   2005

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  • Coordinate regulation of cell growth and differentiation by TGF-β superfamily and Runx proteins. Reviewed

    Miyazono K, Maeda S, Imamura T.

    Oncogene   23   4232 - 4237   2004

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  • 骨形成と骨吸収の分子メカニズム-TGF-β/BMPシグナルを中心に- Reviewed

    前田真吾、小宮節郎

    先端医療シリーズ22・整形外科 整形外科の最新医療(編集主幹 平澤泰介・井上一・高岡邦夫、編集委員 小宮節郎・久保俊一・戸山芳昭・中村利孝・中村孝志・安田和則), 先端医療技術研究所発行   31 - 37   2003

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  • ソルチリン

    前田真吾

    整形外科   54 ( 9 )   1224   2003

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  • TGF-βシグナルとその制御-分子標的治療を目指して-

    今村健志, 前田真吾, 宮園浩平

    現代医療   35 ( 12 )   58 - 64   2003

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  • TGF-β/BMPシグナルと骨芽細胞分化

    前田真吾、今村健志、宮園浩平

    実験医学増刊   20   101(2517) - 112(2528)   2002

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  • 脊椎靭帯における分子生物学. Reviewed

    松永俊二, 前田真吾, 古賀公明, 井ノ上逸朗, 小宮節郎, 酒匂崇.

    関節外科   21   232 - 235   2002

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  • 脊椎後縦靭帯骨化症(OPLL)の遺伝解析・機能解析. Reviewed

    前田真吾, 古賀公明, 小宮節郎.

    骨・関節・靭帯   14   1039 - 1041   2001

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  • 後縦靭帯骨化の病因論-最近の進歩. Reviewed

    古賀公明, 米和徳, 前田真吾, 松永俊二, 酒匂崇, 井ノ上逸朗.

    脊椎脊髄ジャーナル   12   461 - 469   1999

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Presentations

  • 前田真吾   BMP-誘導因子による軟骨・骨代謝制御   Invited

    第2回JCRベーシックリサーチカンファレンス  一般社団法人日本リウマチ学会

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    Event date: 2015.10

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:東京都  

  • 1,2Yahiro, Y; +1Maeda, S; 1,2Shinohara, N; 1,2Matsuyama, K; 2Kawamura, I; 2Setoguchi, T; 1,2Nagano, S; 2Yokouchi, M; 1Ishidou, Y; 1,2Komiya, S   Myc Target 1 (MYCT1) Gene is a Novel Target of TGF-β Signaling to Promote Differentiation of Chondrosarcoma Cells   International conference

    Orthopedic Research Society 2015 Annual Meeting  Orthopedic Research Society 2015 Annual Meeting

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    Event date: 2015.3

    Language:English  

    Venue:アメリカ合衆国、ラスベガス市  

    国際学会

  • 1,2Shinohara, N; +1Maeda, S; 1,2Matsuyama, K; 1,2Yahiro, Y; 2Imamura, K; 2Kawamura, I; 2Setoguchi, T; 1,2Nagano, S; 2Yokouchi, M; 1Ishidou, Y; 1,2Komiya, S   Bone Morphogenetic Protein (BMP) Signaling Induces the Imprinted Paternally Expressed Gene 10 (PEG10) to Regulate Expression of Matrix Metalloproteinase (MMP)-1 and -13 in Chondrosarcoma Cells   International conference

    Orthopedic Research Society 2015 Annual Meeting  Orthopedic Research Society 2015 Annual Meeting

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    Event date: 2015.3

    Language:English  

    Venue:アメリカ合衆国、ラスベガス市  

    国際学会

  • Naohiro Shinohara1,2, Shingo Maeda1, Katsuyuki Imamura2, Kanehiro Matsuyama1,2, Masahiro Yokouchi2, Satoshi Nagano2, Takao Setoguchi3, Yasuhiro Ishidou1, Setsuro Komiya1,2,3   BMP-induced PEG10 is highly expressed in chondrosarcoma cells to suppress BMP signaling-mediated expression of matrix metalloproteinase (MMP)-1/13 and cell invasion  

    第28回日本軟骨代謝学会  第28回日本軟骨代謝学会

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    Event date: 2015.3

    Language:Japanese  

    Venue:東京都  

    国内学会

  • Shingo Maeda, Naohiro Shinohara, Masahiro Yokouchi, Satoshi Nagano, Yasuhiro Ishidou, Setsuro Komiya   BMP-induced PEG10 regulates level of metalloproteinases and invasion of chondrosarcoma cells   International conference

    Joint International Symposium on TGF-β Family and Cancer: Signal Network in Tumor Microenvironment 

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    Event date: 2015.1

    Language:English   Presentation type:Poster presentation  

    Venue:Tsukuba, Japan  

  • Shingo Maeda, Naohiro Shinohara, Masahiro Yokouchi, Satoshi Nagano, Yasuhiro Ishidou, Setsuro Komiya   BMP-induced PEG10 regulates level of metalloproteinases and invasion of chondrosarcoma cells   International conference

    Joint International Symposium on TGF-b Family and Cancer  Joint International Symposium on TGF-b Family and Cancer

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    Event date: 2015.1

    Language:English  

    Venue:つくば市  

    国際学会

  • 篠原直弘1,2、前田真吾1、今村勝行1,2、松山金寛1,2、横内雅博2、石堂康弘1、小宮節郎1 ,2   軟骨肉腫細胞株で高発現するインプリンティング遺伝子PEG10はTGF-βファミリー・シグナルとMMP発現を制御する  

    第37回日本分子生物学会年会  第37回日本分子生物学会年会

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    Event date: 2014.11

    Language:Japanese  

    Venue:横浜市  

    国内学会

  • 栫 博則1,2、前田 真吾1、篠原 直弘1,2、松山 金寛1,2、今村 勝行1,2、河村 一郎2、横内 雅博2、石堂康弘1、小宮節郎1,2   Runx2依存的に軟骨細胞成熟時に誘導されるnSMase2はAkt経路とHas2発現の制御を介して軟骨細胞成熟を抑制する  

    第29回日本整形外科学会基礎学術集会  第29回日本整形外科学会基礎学術集会

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    Event date: 2014.10

    Language:Japanese  

    Venue:鹿児島市  

    国内学会

  • 今村 勝行1,2、前田 真吾1、河村 一郎2、松山 金寛1 ,2、篠原 直弘1 ,2、八尋 雄平1 ,2、石堂 康弘1、小宮 節郎1 ,2   Alg2はRunx2の機能を抑制して骨形成を抑制し、軟骨においてはCreb3l2発現と分化を抑制する  

    第29回日本整形外科学会基礎学術集会  第29回日本整形外科学会基礎学術集会

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    Event date: 2014.10

    Language:Japanese  

    Venue:鹿児島市  

    国内学会

  • 篠原直弘1,2、前田真吾1、今村勝行1,2、松山金寛1,2、横内雅博2、石堂康弘1、小宮節郎1 ,2   哺乳類特異的遺伝子PEG10はTGF-βファミリー・シグナルを制御し軟骨細胞と軟骨肉腫細胞の分化度に影響する  

    第29回日本整形外科学会基礎学術集会  第29回日本整形外科学会基礎学術集会

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    Event date: 2014.10

    Language:Japanese  

    Venue:鹿児島市  

    国内学会

  • 前田真吾1, 河村一郎1,2, 今村勝行1,2, 栫博則1,2, 松山金寛1,2, 篠原直弘1,2, 横内雅博2, 石堂康弘1, 小宮節郎1,2   軟骨細胞の分化成熟を制御する分子機構の同定と解析  

    第29回日本整形外科学会基礎学術集会  第29回日本整形外科学会基礎学術集会

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    Event date: 2014.10

    Language:Japanese  

    Venue:鹿児島市  

    国内学会

  • 篠原直弘1,2, 前田真吾1, 今村勝行1,2, 松山金寛1,2,横内雅博2, 石堂康弘1, 小宮節郎1 ,2   TGF-βファミリー・シグナルの軟骨細胞と軟骨肉腫細胞への影響における父性インプリンティング遺伝子PEG10の役割  

    第15回運動器科学研究会  第15回運動器科学研究会

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    Event date: 2014.9

    Language:Japanese  

    Venue:東京都  

    国内学会

  • Naohiro Shinohara, Shingo Maeda, Masahiro Yokouchi, Takao Setoguchi, Satoshi Nagano, Setsuro Komiya   An imprinting gene, paternally expressed gene 10, is overexpressed in chondrosarcoma cells to regulate TGF-β family signaling and status of the chondrogenic differentiation  

    第73回日本癌学会  第73回日本癌学会

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    Event date: 2014.9

    Language:Japanese  

    Venue:横浜市  

    国内学会

  • 篠原直弘1,2、前田真吾1、今村勝行1,2、松山金寛1,2、横内雅博2、石堂康弘1、小宮節郎1 ,2   父性インプリンティング遺伝子PEG10のTGF-βファミリー・シグナル調節と軟骨細胞・軟骨肉腫細胞の分化度に対する役割  

    第32回日本骨代謝学会  第32回日本骨代謝学会

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    Event date: 2014.7

    Language:Japanese  

    Venue:大阪市  

    国内学会

  • 今村勝行1,2、前田真吾1、河村一郎2、松山金寛1,2、篠原直弘1,2、八尋雄平1,2、石堂康弘1、小宮節郎1,2   Alg2はHivep3の骨形成と軟骨形成のuncoupling機能を担う下流因子である  

    第32回日本骨代謝学会  第32回日本骨代謝学会

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    Event date: 2014.7

    Language:Japanese  

    Venue:大阪市  

    国内学会

  • 栫 博則1,2、前田 真吾1、篠原 直弘1,2、松山 金寛1,2、今村 勝行1,2、河村 一郎2、横内 雅博2、石堂康弘1、小宮節郎1,2   BMPシグナルによりRunx2依存的に誘導されるnSMase2はセラミドを介してAkt経路と軟骨細胞成熟を抑制する  

    第32回日本骨代謝学会  第32回日本骨代謝学会

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    Event date: 2014.7

    Language:Japanese  

    Venue:大阪市  

    国内学会

  • Shingo Maeda   TGF-β Family Signaling Regulates Expression of Paternally Expressed 10 in Chondrogenesis   International conference

    TGF-β Meeting 2014:‘TGF-β signal transduction in human disease’  TGF-β Meeting 2014:‘TGF-β signal transduction in human disease’

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    Event date: 2014.5

    Language:English  

    Venue:オランダ、ライデン市  

    国際学会

  • 今村勝行1,2、前田真吾1、篠原直弘1,2、松山金寛1,2、河村一郎2、横内雅博2、石堂康弘1、小宮節郎1 ,2   Human immunodeficiency virus type Ⅰ enhancer binding protein 3 (Hivep3)の下流として同定したAsparagine-linked glycosylation 2 (Alg2)は骨芽細胞と軟骨細胞の分化を調節する  

    第27回日本軟骨代謝学会  第27回日本軟骨代謝学会

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    Event date: 2014.2

    Language:Japanese  

    Venue:京都市  

    国内学会

  • 前田 真吾1、栫 博則1,2、篠原 直弘1,2、松山 兼寛1,2、今村 勝行1,2、河村 一郎2、横内 雅博2、石堂康弘1、小宮節郎1,2   BMPシグナルにより誘導されるSmpd3はセラミド-Akt経路を介して軟骨細胞分化成熟を抑制する  

    第27回日本軟骨代謝学会  第27回日本軟骨代謝学会

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    Event date: 2014.2

    Language:Japanese  

    Venue:京都市  

    国内学会

  • 篠原直弘1,2、前田真吾1、今村勝行1,2、松山金寛1,2、横内雅博2、石堂康弘1、小宮節郎1 ,2   インプリンティング遺伝子Peg10の軟骨細胞分化における役割  

    第27回日本軟骨代謝学会  第27回日本軟骨代謝学会

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    Event date: 2014.2

    Language:Japanese  

    Venue:京都市  

    国内学会

  • 前田真吾1、栫博則2、松山金寛1, 2、河村一郎2、今村勝行1, 2、篠原直弘1, 2、永野聡2、瀬戸口啓夫3、横内雅博2、石堂康弘1、小宮節郎1, 2   BMP-2シグナルはneutral sphingomyelinase 2の誘導によるAktシグナル経路の抑制を介して軟骨細胞分化成熟を制御する  

    第36回日本分子生物学会年会  第36回日本分子生物学会年会

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    Event date: 2013.12

    Language:Japanese  

    Venue:神戸市  

    国内学会

  • 篠原直弘1, 2、前田真吾1、今村勝行1, 2、松山金寛1, 2、河村一郎2、横内雅博2、石堂康弘1、小宮節郎1, 2   インプリンティング遺伝子Peg10はBMP-2誘導の骨・軟骨細胞分化を促進する  

    第36回日本分子生物学会年会  第36回日本分子生物学会年会

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    Event date: 2013.12

    Language:Japanese  

    Venue:神戸市  

    国内学会

  • Shingo Maeda, Hironori Kakoi, Kanehiro Matsuyama, Ichiro Kawamura, Katsuyuki Imamura, Naohiro Shinohara, Satoshi Nagano, Takao Setoguchi, Masahiro Yokouchi, Yasuhiro Ishidou, and Setsuro Komiya   BMP-2-induced nSMase2 suppresses chondrocyte maturation   International conference

    The 3rd International Symposium by JSPS Core-to-Core Program “Cooperative International Framework in TGF-β Family Signaling”  The 3rd International Symposium by JSPS Core-to-Core Program “Cooperative International Framework in TGF-β Family Signaling”

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    Event date: 2013.10

    Language:English  

    Venue:松山市  

    国際学会

  • Shingo Maeda1, Hironori Kakoi2, Kanehiro Matsuyama1,2, Katsuyuki Imamura1,2, Ichiro Kawamura2, Naohiro Shinohara1,2, Masahiro Yokouchi2, Yasuhiro Ishidou1, Setsuro Komiya1,2   Neutral Sphingomyelinase 2 Is Increased During BMP-induced Differentiation of ATDC5 Chondrocytes to Suppress the Maturation as a Negative Feedback Mechanism   International conference

    The American Society for Bone and Mineral Research 2013  The American Society for Bone and Mineral Research 2013

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    Event date: 2013.10

    Language:English  

    Venue:Baltimore, USA  

    国際学会

  • 栫博則1,2、前田真吾1、松山兼寛1,2、今村勝行1,2、河村一郎2、篠原直弘1,2、横内雅博2、石堂康弘1、小宮節郎1,2   Smpd3/nSMase2はセラミドを介したAktシグナル経路阻害によりATDC5軟骨細胞分化とヒアルロン酸合成酵素Has2の発現を抑制する  

    第28回日本整形外科学会基礎学術集会  第28回日本整形外科学会基礎学術集会

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    Event date: 2013.10

    Language:Japanese  

    Venue:千葉市  

    国内学会

  • 今村勝行1, 2、前田真吾1、河村一郎2、石堂康弘1、横内雅博2、小宮節郎1, 2   Schnurriファミリーによる骨芽細胞分化調節の多様性  

    第28回日本整形外科学会基礎学術集会  第28回日本整形外科学会基礎学術集会

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    Event date: 2013.10

    Language:Japanese  

    Venue:千葉市  

    国内学会

  • 篠原直弘1, 2、前田真吾1、今村勝行1, 2、松山金寛1, 2、河村一郎2、横内雅博2、石堂康弘1、小宮節郎1, 2   インプリンティング遺伝子Peg10の骨芽細胞と軟骨細胞の分化への関与  

    第28回日本整形外科学会基礎学術集会  第28回日本整形外科学会基礎学術集会

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    Event date: 2013.10

    Language:Japanese  

    Venue:千葉市  

    国内学会

  • Katsuyuki Imamura, Shingo Maeda, Ishidou Yasuhiro, Masahiro Yokouchi, Setsuro Komiya   The roles of Schnurri family in differentiation of osteoblasts and chondrocytes   International conference

    Australian and New Zealand Bone and Mineral Society 23rd ANNUAL SCIENTIFIC MEETING  Australian and New Zealand Bone and Mineral Society 23rd ANNUAL SCIENTIFIC MEETING

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    Event date: 2013.9

    Language:English  

    Venue:Melbourne, Australia  

    国際学会

  • 前田真吾   BMP シグナルがRunx2依存的に誘導するSmpd3/nSMase2は、セラミド・シグナルによるAkt 経路の抑制によって軟骨細胞分化とHas2発現を抑制する  

    第14回運動器科学研究会  第14回運動器科学研究会

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    Event date: 2013.9

    Language:Japanese  

    Venue:東京都  

    国内学会

  • Shingo Maeda1, Hironori Kakoi1,2, Kanehiro Matsuyama1,2, Ichiro Kawamura1,2, Katsuyuki Imamura1,2, Naohiro Shinohara1,2, Masahiro Yokouchi2, Yasuhiro Ishidou1, and Setsuro Komiya1,2   BMP signaling induces sphingomyelin phosphodiesterase 3 to suppress chondrocyte maturation and expression of hyaluronan synthase 2 in ATDC5 chondrocytes   International conference

    TGF-β meeting in Uppsala  TGF-β meeting in Uppsala

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    Event date: 2013.5

    Language:English  

    Venue:Uppsala, Sweden  

    国際学会

  • Hironori Kakoi1,2, Shingo Maeda1, Ichiro Kawamura2, Katsuyuki Imamura1,2, Naohiro Shinohara1,2, Masahiro Yokouchi2, Yasuhiro Ishidou1, Setsuro Komiya1,2   4. Smpd3/nSMase2 suppresses Akt signaling pathway to inhibit chondrogenic differentiation and expression of Has2 in ATDC5 cells  

    国際骨代謝学会・日本骨代謝学会 第2回合同国際会議  国際骨代謝学会・日本骨代謝学会 第2回合同国際会議

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    Event date: 2013.5

    Language:Japanese  

    Venue:神戸市  

    国内学会

  • Imamura K1,2, Maeda S1, Kawamura I1,2, Ishidou Y1, Yokouchi M2 and Komiya S1,2   Alg2 is induced by Schnurri-3 to inhibit transcriptional activity of Runx2 and osteoblast differentiation   International conference

    ESCEO-IOF13  ESCEO-IOF13

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    Event date: 2013.4

    Language:English  

    Venue:ローマ、イタリア  

    国際学会

  • 栫 博則1,2、前田 真吾1、篠原 直弘1,2、松山 兼寛1,2、今村 勝行1,2、河村 一郎2、横内 雅博2、石堂康弘1、小宮節郎1,2   Smpd3はATDC5軟骨細胞分化とHas2発現を抑制する  

    第26回 日本軟骨代謝学会  第26回 日本軟骨代謝学会

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    Event date: 2013.3

    Language:Japanese  

    Venue:大阪府 豊中市  

    国内学会

  • 今村 勝行1,2、前田 真吾1、河村 一郎2、石堂 康弘1、横内 雅博2、小宮 節郎1 ,2   骨軟骨細胞分化におけるSchnurri familyの役割  

    第26回 日本軟骨代謝学会  第26回 日本軟骨代謝学会

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    Event date: 2013.3

    Language:Japanese  

    Venue:大阪府 豊中市  

    国内学会

  • Imamura, Katsuyuki1, 2; Maeda, Shingo1; Kawamura, Ichiro1, 2; Yokouchi, Masahiro2; Ishidou, Yasuhiro1; Komiya, Setsuro1, 2   Asparagine-linked glycosylation 2 homolog, identified as a downstream target of Schnurri-3, cell-autonomously regulates differentiation of osteoblasts and chondrocytes.   International conference

    2013 Annual Meeting of Orthopaedic Research Society  2013 Annual Meeting of Orthopaedic Research Society

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    Event date: 2013.1

    Language:English  

    Venue:San Antonio, Texas, USA  

    国際学会

  • 1,2Kawamura, I; +1Maeda, S; 1,2Imamura, K; 2Yokouchi, M; 1Ishidou, Y; 1,2Komiya, S   TGF-β signaling is highly active to induce SnoN in ectopically hypertrophying chondrocytes in degenerating osteoarthritis cartilage. - Evaluating SnoN as a molecular target for regulating progression of chondrocyte maturation -   International conference

    2013 Annual Meeting of Orthopaedic Research Society  2013 Annual Meeting of Orthopaedic Research Society

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    Event date: 2013.1

    Language:English  

    Venue:San Antonio, Texas, USA  

    国際学会

  • Katsuyuki Imamura1,2 , Shingo Maeda1, Ichiro Kawamura1,2, Masahiro Yokouchi2, Yasuhiro Ishidou1, Setsuro Komiya1,2   Alg2, identified as a downstream mediator of Schnurri-3, regulates differentiation of osteoblasts and chondrocytes negatively and positively, respectively.  

    第35回 日本分子生物学会  第35回 日本分子生物学会

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    Event date: 2012.12

    Language:Japanese  

    Venue:福岡市  

    国内学会

  • Shingo Maeda1, Ichiro Kawamura1,2, Katsuyuki Imamura1,2, Masahiro Yokouchi2, Yasuhiro Ishidou1, Setsuro Komiya1,2   SnoN mediates a signal crosstalk between TGF-β and BMP pathways in chondrocytes to prevent hypertrophic maturation   International conference

    The 2nd International Symposium by JSPS Core-to-Core Program “Cooperative International Framework in TGF-β Family Signaling”  The 2nd International Symposium by JSPS Core-to-Core Program “Cooperative International Framework in TGF-β Family Signaling”

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    Event date: 2012.10

    Language:English  

    Venue:東京都  

    国際学会

  • 前田 真吾1) 今村 勝行1)2) 栫博則1)2) 河村 一郎1)2)横内 雅博2) 石堂 康弘1) 小宮 節郎1)2)   シンポジウム7 骨形成研究最前線 骨芽細胞分化と骨形成の分子制御の最新知見 1  

    第27回 日本整形外科学会基礎学術集会  第27回 日本整形外科学会基礎学術集会

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    Event date: 2012.10

    Language:Japanese  

    Venue:名古屋市  

    国内学会

  • 前田真吾   Smpd3/nSMase2のATDC5軟骨細胞分化における役割  

    第13回 運動器科学研究会  第13回 運動器科学研究会

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    Event date: 2012.9

    Language:Japanese  

    Venue:京都市  

    研究会

  • Kakoi H, Maeda S, Kawamura I, Imamura K, Yokouchi M, Ishidou Y, and Komiya S   Sphingomyelin phosphodiesterase 3 negatively regulates expression of chondrogenic marker genes and hyaluronan synthase 2 in ATDC5 chondrocytes.   International conference

    1st Asia-Pacific Bone and Mineral Research Meeting with the ANZBMS 22nd Annual Scientific Meeting  1st Asia-Pacific Bone and Mineral Research Meeting with the ANZBMS 22nd Annual Scientific Meeting

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    Event date: 2012.9

    Language:English  

    Venue:Perth, Western Australia, Australia  

    国際学会

  • Imamura K, Maeda S, Kawamura I, Ishidou Y, Yokouchi M, and Komiya S   Alg2, identified as a downstream mediator of Schnurri-3, inhibits function of Runx2 and osteoblast differentiation   International conference

    1st Asia-Pacific Bone and Mineral Research Meeting with the ANZBMS 22nd Annual Scientific Meeting  1st Asia-Pacific Bone and Mineral Research Meeting with the ANZBMS 22nd Annual Scientific Meeting

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    Event date: 2012.9

    Language:English  

    Venue:Perth, Western Australia, Australia  

    国際学会

  • Ichiro Kawamura, Shingo Maeda, Katsuyuki Imamura, Masahiro Yokouchi, Yasuhiro Ishidou, and Setsuro Komiya   SnoN mediates a crosstalk between TGF-β and BMP signaling to suppress hypertrophic maturation of chondrocytes   International conference

    1st Asia-Pacific Bone and Mineral Research Meeting with the ANZBMS 22nd Annual Scientific Meeting  1st Asia-Pacific Bone and Mineral Research Meeting with the ANZBMS 22nd Annual Scientific Meeting

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    Event date: 2012.9

    Language:English  

    Venue:Perth, Western Australia, Australia  

    国際学会

  • 河村 一郎, 前田 真吾, 今村 勝行, 横内 雅博, 石堂 康弘, 小宮 節郎   軟骨細胞肥大分化成熟期におけるTGF-βシグナルとBMPシグナルのクロストーク  

    第30回日本骨代謝学会  第30回日本骨代謝学会

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    Event date: 2012.7

    Language:Japanese  

    Venue:東京都  

    国内学会

  • 今村 勝行, 前田 真吾, 河村 一郎, 横内 雅博, 石堂 康弘, 小宮 節郎   Schnurri-3の下流因子として同定したAlg2はRunx2機能を阻害し骨芽細胞分化を抑制する  

    第30回日本骨代謝学会  第30回日本骨代謝学会

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    Event date: 2012.7

    Language:Japanese  

    Venue:東京都  

    国内学会

  • 前田真吾   BMP-2添加により誘導されるSphingomyelin phosphodiesterase 3はATDC5軟骨細胞分化とHyaluronan synthase 2の発現を抑制する  

    第19回BMP研究会  第19回BMP研究会

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    Event date: 2012.7

    Language:Japanese  

    Venue:東京都  

    研究会

  • Kawamura I, Maeda S, Imamura K, Yokouchi M, Ishidou Y, Komiya S   Endogenous TGF-β-induced SnoN prevents BMP signaling and subsequent hypertrophic differentiation of chondrocytes   International conference

    The 22nd Japanese-Korean Combined Orthopaedic Symposium  The 22nd Japanese-Korean Combined Orthopaedic Symposium

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    Event date: 2012.6

    Language:English  

    Venue:栃木県  

    国際学会

  • Katsuyuki Imamura, Ichiro Kawamura, Yasuhiro Ishidou, Masahiro Yokouchi, Shingo Maeda, Setsuro Komiya   Mannosyltransferase Alg2, identified as a downstream mediator of Schnurri-3, is involved in differentiation of osteoblast and chondrocyte.  

    第25回日本軟骨代謝学会  第25回日本軟骨代謝学会

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    Event date: 2012.3

    Language:Japanese  

    Venue:愛知  

    国内学会

  • Ichiro Kawamura, Yasuhiro Ishidou, Katsuyuki Imamura, Masahiro Yokouchi, Shingo Maeda, Setsuro Komiya   SnoN, a target of TGF-β signaling, inhibits BMP-induced hypertrophic conversion of chondrocytes.  

    第25回日本軟骨代謝学会  第25回日本軟骨代謝学会

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    Event date: 2012.3

    Language:Japanese  

    Venue:愛知  

    国内学会

  • Kawamura, I; Ishidou, Y; Imamura, K; Yokouchi, M; Komiya, S; Maeda, S.   SnoN mediates a signal crosstalk between TGF-β and BMP in maturating chondrocytes.  

    第34回日本分子生物学会年会  第34回日本分子生物学会年会

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    Event date: 2011.12

    Language:Japanese  

    Venue:神奈川  

    国内学会

  • Katsuyuki Imamura, Yasuhiro Ishidou, Ichiro Kawamura, Masahiro Yokouchi, Setsuro Komiya, Shingo Maeda.   Mannosyltransferase Alg2 regulates differentiation of osteoblasts and chondrocytes.  

    第34回日本分子生物学会年会  第34回日本分子生物学会年会

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    Event date: 2011.12

    Language:Japanese  

    Venue:神奈川  

    国内学会

  • 今村勝行, 石堂康弘, 河村一郎, 横内雅博, 小宮節郎, 前田真吾   骨芽細胞分化を抑制するSchnurri-3は軟骨細胞分化を促進する   International conference

    第26回日本整形外科学会基礎学術集会  第26回日本整形外科学会基礎学術集会

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    Event date: 2011.10

    Language:English  

    Venue:群馬  

    国際学会

  • 河村 一郎 石堂 康弘 今村 勝行 横内 雅博 小宮 節郎 前田 真吾   軟骨細胞肥大分化過程におけるSnoNの機能解析と変形性関節症との関連   International conference

    第26回日本整形外科学会基礎学術集会  第26回日本整形外科学会基礎学術集会

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    Event date: 2011.10

    Language:English  

    Venue:群馬  

    国際学会

  • Ichiro Kawamura, Yasuhiro Ishidou, Katsuyuki Imamura, Masahiro Yokouchi, Setsuro Komiya, Shingo Maeda   TGF-β-induced SnoN prevents BMP signaling and hypertrophic conversion of chondrocytes.   International conference

    ASBMR(American Society for Bone and Mineral Research)2011  ASBMR(American Society for Bone and Mineral Research)2011

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    Event date: 2011.9

    Language:English  

    Venue:アメリカ合衆国  

    国際学会

  • Katsuyuki Imamura, Yasuhiro Ishidou, Ichiro Kawamura, Masahiro Yokouchi, Setsuro Komiya, Shingo Maeda.   Mannosyltransferase Alg2 is a downstream regulator of Schnurri-3 in osteoblast differentiation.   International conference

    ASBMR(American Society for Bone and Mineral Research)2011  ASBMR(American Society for Bone and Mineral Research)2011

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    Event date: 2011.9

    Language:English  

    Venue:アメリカ合衆国  

    国際学会

  • 前田 真吾、今村 勝行、石堂 康弘、河村 一郎、横内 雅博、小宮 節郎   骨芽細胞と軟骨細胞の分化における Schnurri-3 の役割  

    第12回運動器科学研究会  第12回運動器科学研究会

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    Event date: 2011.9

    Language:Japanese  

    Venue:高知  

    研究会

  • 河村 一郎、石堂 康弘、今村 勝行、横内 雅博、小宮 節郎、前田 真吾   軟骨細胞分化成熟におけるSnoNの発現と機能  

    第29回日本骨代謝学会  第29回日本骨代謝学会

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    Event date: 2011.7

    Language:Japanese  

    Venue:大阪  

    国内学会

  • 今村 勝行、石堂 康弘、河村 一郎、横内 雅博、小宮 節郎、前田 真吾   Schnurri-3の下流因子として同定した糖転移酵素Alg2は骨芽細胞分化を抑制する  

    第29回日本骨代謝学会  第29回日本骨代謝学会

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    Event date: 2011.7

    Language:Japanese  

    Venue:大阪  

    国内学会

  • 今村 勝行、石堂 康弘、河村 一郎、山元 拓哉、善明 美千久、井尻 幸成、小宮 節郎、前田 真吾   骨芽細胞分化と軟骨細胞分化におけるSchnurri-3の役割  

    第24回日本軟骨代謝学会  第24回日本軟骨代謝学会

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    Event date: 2011.3

    Language:Japanese  

    Venue:福岡  

    国内学会

  • 河村 一郎、石堂 康弘、今村 勝行、瀬戸口 啓夫、山元 拓哉、善明 美千久、井尻 幸成、小宮 節郎、前田 真吾   Oncogene SnoNの軟骨細胞成熟肥大過程における機能解析と変形性関節症との関連  

    第24回日本軟骨代謝学会  第24回日本軟骨代謝学会

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    Event date: 2011.3

    Language:Japanese  

    Venue:福岡  

    国内学会

  • Kawamura, I, Ishidou, Y, Setoguchi, T, Yamamoto, T, Zenmyo, M, Ijiri, K, Komiya, S, Maeda, S.   Screening of Molecular Effectors Responsible for the Suppression of Col10a1 Gene Expression by TGF-beta Signaling in Chondrocytes.   International conference

    2011 Orthopaedic Research Society Annual Meeting  2011 Orthopaedic Research Society Annual Meeting

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    Event date: 2011.1

    Language:English  

    Venue:アメリカ合衆国  

    国際学会

  • Maeda, S, Kawamura, I, Ishidou, Y, Setoguchi, T, Yamamoto, T, Zenmyo, M, Ijiri, K, Komiya, S.   Chondrocyte Differentiation is Suppressed by Knock-down of Schnurri-3 Gene In Vitro.   International conference

    2011 Orthopaedic Research Society Annual Meeting  2011 Orthopaedic Research Society Annual Meeting

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    Event date: 2011.1

    Language:English  

    Venue:アメリカ合衆国  

    国際学会

  • 前田真吾   SnoNはBMP誘導軟骨分化成熟を抑制する.  

    第33回日本分子生物学会年会(BMB2010)  第33回日本分子生物学会年会(BMB2010)

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    Event date: 2010.12

    Language:Japanese  

    Venue:兵庫  

    国内学会

  • 河村一郎、石堂康弘、山元拓哉、瀬戸口啓夫、善明美千久、小宮節郎、前田真吾   TGF-βシグナル阻害剤SB431542は前駆軟骨細胞株ATDC5のBMP誘導軟骨分化を促進する  

    第25回日本整形外科学会基礎学術集会  第25回日本整形外科学会基礎学術集会

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    Event date: 2010.10

    Language:Japanese  

    Venue:京都  

    国内学会

  • Shingo Maeda   BMP-2 regulates osteoclast differentiation through Jmjd1a-dependent activation of Hesr1 and Hesr3  

    6th Meeting of Bone Biology Forum  6th Meeting of Bone Biology Forum

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    Event date: 2009.8

    Language:Japanese  

    Venue:静岡  

    研究会

  • 前田真吾   前田真吾:Hesr1とHesr3は骨芽細胞のOsteoprotegerin発現促進を介して骨吸収を制御し骨量を維持する  

    第26回 日本骨代謝学会学術集会  第26回 日本骨代謝学会学術集会

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    Language:Japanese  

    Venue:大阪  

    国内学会

  • 前田真吾、小久保博樹、油谷浩幸、小宮節郎、宮園浩平   Hesr1とHesr3は相補的に骨芽細胞分化・骨量を制御する  

    BMB2007 (第30回 日本分子生物学会・第80回 日本生化学会大会 合同大会)  BMB2007 (第30回 日本分子生物学会・第80回 日本生化学会大会 合同大会)

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    Language:Japanese  

    Venue:神奈川  

    国内学会

  • 前田真吾、小久保博樹、小宮節郎、宮園浩平、今村健志   Hey1とHeyLは相補的に骨芽細胞分化を制御する  

    第22回 日本整形外科学会基礎学術集会  第22回 日本整形外科学会基礎学術集会

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    Language:Japanese  

    Venue:静岡  

    国内学会

  • 前田真吾、林真琴、小宮節郎、今村健志、宮園浩平   内因性TGF-βシグナルは間葉系前駆細胞の骨芽細胞分化成熟を抑制する  

    第78回 日本整形外科学会学術総会  第78回 日本整形外科学会学術総会

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    Language:Japanese  

    Venue:神奈川  

    国内学会

  • 前田真吾、小宮節郎、今村健志、宮園浩平   骨芽細胞分化におけるBMPシグナルとTGF-βシグナルのクロストークと腫瘍性骨形成抑制の可能性  

    第19回 日本整形外科学会基礎学術集会  第19回 日本整形外科学会基礎学術集会

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    Language:Japanese  

    Venue:東京  

    国内学会

  • Maeda S., Kokubo H., Aburatani H., Nomura S., Komiya S., Miyazono K., Imamura T.   Endogenous Hesr/Hey Genes Redundantly Support Osteoblast Differentiation.   International conference

    29th Annual Meeting of the American Socienty for Bone and Mineral Research  29th Annual Meeting of the American Socienty for Bone and Mineral Research

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    Language:English  

    Venue:アメリカ合衆国  

    国際学会

  • Maeda S., Hanyu A., Miyazono K., Imamura T.   Identification of Novel Target Genes of Runx2 in Bone Metastasis of Breast Cancer Cells.   International conference

    The 11th Japan-Korea Cancer Research Workshop  The 11th Japan-Korea Cancer Research Workshop

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    Language:English  

    Venue:韓国  

    国際学会

  • Maeda S., Hayashi M., Shirakawa K., Komiya S., Imamura T., Miyazono K.   Inhibition of Endogenous TGF-β Signaling Accelerates Maturation of Osteoblast Differentiation from Mesenchymal Progenitors.   International conference

    The 26th Annual Meeting of the American Society for Bone and Mineral Research  The 26th Annual Meeting of the American Society for Bone and Mineral Research

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    Language:English  

    Venue:アメリカ合衆国  

    国際学会

  • 八尋 雄平, 前田 真吾, 森川 真大, 鯉沼 代造, 篠原 直弘, 河村 一郎, 佐久間 大輔, 城光寺 豪, 影山 龍一郎, 宮園 浩平, 小宮 節郎   BMPシグナル標的遺伝子Atoh8はマウス成獣の骨量を増加させる  

    日本骨代謝学会学術集会プログラム抄録集  2018.7  (一社)日本骨代謝学会

  • 篠原 直弘, 前田 真吾, 永野 聡, 瀬戸口 啓夫, 石堂 康弘, 小宮 節郎   TGF-betaにより活性化されるSMADとPEG10は互いに抑制しあい二層性の役割を持つ  

    日本癌学会総会記事  2017.9  (一社)日本癌学会

  • 篠原 直弘, 前田 真吾, 八尋 雄平, 河村 一郎, 永野 聡, 石堂 康弘, 小宮 節郎   PEG10とTGF-βシグナルの軟骨肉腫表現型における役割  

    日本整形外科学会雑誌  2017.3  (公社)日本整形外科学会

  • 八尋 雄平, 前田 真吾, 森川 真大, 鯉沼 代造, 佐久間 大輔, 篠原 直弘, 松山 金寛, 河村 一郎, 石堂 康弘, 影山 龍一郎, 宮園 浩平, 小宮 節郎   BMP誘導因子Atoh8の欠損は骨量を減少させる  

    日本整形外科学会雑誌  2017.8  (公社)日本整形外科学会

  • 八尋 雄平, 前田 真吾, 森川 真大, 鯉沼 代造, 篠原 直弘, 河村 一郎, 佐久間 大輔, 石堂 康弘, 影山 龍一郎, 宮園 浩平, 小宮 節郎   BMPシグナル標的遺伝子Atoh8欠損マウスの骨量は減少する  

    日本骨代謝学会学術集会プログラム抄録集  2017.7  (一社)日本骨代謝学会

  • 立花 直寛, 千々松 良太, 谷口 優樹, 尾市 健, 加藤 壯, 松林 嘉孝, 大島 寧, 矢野 文子, 前田 真吾, 田中 栄, 齋藤 琢   頸椎後縦靱帯骨化症の発症における疾患感受性遺伝子RSPO2の役割  

    日本整形外科学会雑誌  2020.9  (公社)日本整形外科学会

  • 篠原 直弘, 前田 真吾, 八尋 雄平, 佐久間 大輔, 石堂 康弘, 永野 聡, 小宮 節郎   軟骨肉腫におけるTGF-βシグナルとPEG10の発現と役割  

    日本整形外科学会雑誌  2017.8  (公社)日本整形外科学会

  • 前田 真吾, 城光寺 豪, 伊集院 俊郎, 河村 一郎, 今村 勝行, 栫 博則, 篠原 直弘, 八尋 雄平, 谷口 昇   軟骨代謝研究の最前線 BMPシグナルと骨軟骨代謝  

    日本整形外科学会雑誌  2020.9  (公社)日本整形外科学会

  • 城光寺 豪, 前田 真吾, 中島 正宏, 河村 一郎, 八尋 雄平, 冨永 博之, 武冨 榮二, 池川 志郎, 谷口 昇   脊椎後縦靱帯骨化症原因候補遺伝子CDC5Lは骨芽細胞分化を抑制し、初期軟骨細胞分化を促進する  

    日本整形外科学会雑誌  2020.3  (公社)日本整形外科学会

  • 城光寺 豪, 前田 真吾, 中島 正宏, 河村 一郎, 八尋 雄平, 冨永 博之, 武冨 榮二, 池川 志郎, 谷口 昇   脊椎後縦靱帯骨化症原因候補遺伝子CDC5Lは骨芽細胞分化を抑制し、初期軟骨細胞分化を促進する  

    日本骨代謝学会学術集会プログラム抄録集  2020.10  (一社)日本骨代謝学会

  • 城光寺 豪, 前田 真吾, 中島 正宏, 河村 一郎, 八尋 雄平, 冨永 博之, 武冨 榮二, 池川 志郎, 谷口 昇   脊椎後縦靱帯骨化症原因候補遺伝子CDC5Lは初期軟骨細胞分化を促進する  

    日本整形外科学会雑誌  2020.9  (公社)日本整形外科学会

  • 城光寺 豪, 前田 真吾, 冨永 博之, 八尋 雄平, 河村 一郎, 中島 正宏, 池川 志郎, 谷口 昇   脊椎後縦靱帯骨化症原因候補遺伝子CDC5Lの機能解析  

    日本骨代謝学会学術集会プログラム抄録集  2019.9  (一社)日本骨代謝学会

  • 城光寺 豪, 前田 真吾, 中島 正宏, 河村 一郎, 八尋 雄平, 冨永 博之, 武冨 榮二, 池川 志郎, 谷口 昇   脊椎後縦靱帯骨化症原因候補遺伝子CDC5Lの機能解析  

    日本整形外科学会雑誌  2019.9  (公社)日本整形外科学会

  • 城光寺 豪, 前田 真吾, 中島 正宏, 河村 一郎, 八尋 雄平, 冨永 博之, 武冨 榮二, 池川 志郎, 谷口 昇   脊柱後縦靱帯骨化症関連遺伝子CDC5Lは骨芽細胞分化を抑制する  

    日本整形外科学会雑誌  2019.3  (公社)日本整形外科学会

  • 城光寺 豪, 前田 真吾, 中島 正宏, 河村 一郎, 八尋 雄平, 冨永 博之, 武冨 榮二, 池川 志郎, 谷口 昇   脊柱後縦靱帯骨化症(OPLL)組織にはosteochondral bipotentialな細胞が存在し、GWASによる原因候補遺伝子を発現する  

    日本整形外科学会雑誌  2020.3  (公社)日本整形外科学会

  • 城光寺 豪, 前田 真吾, 大石 一樹, 伊集院 俊郎, 中島 正宏, 俵積田 裕紀, 河村 一郎, 冨永 博之, 武冨 榮二, 池川 志郎, 谷口 昇   脊椎後縦靱帯骨化症原因候補遺伝子であるCDC5LはSOX9、COL2A1、WEE1のpre-mRNAスプライシングを調整し初期軟骨細胞分化と細胞増殖を促進する  

    日本骨代謝学会学術集会プログラム抄録集  2021.10  (一社)日本骨代謝学会

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  • 伊集院 俊郎, 前田 真吾, 城光寺 豪, 俵積田 裕紀, 大石 一樹, 谷口 昇   ラット肩腱板インピンジメント・モデルtendinopathyとHMGB1発現の関連および分子細胞生物学的機能解析  

    日本整形外科学会雑誌  2021.8  (公社)日本整形外科学会

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  • 城光寺 豪, 前田 真吾, 大石 一樹, 伊集院 俊郎, 中島 正宏, 俵積田 裕紀, 河村 一郎, 冨永 博之, 武冨 榮二, 池川 志郎, 谷口 昇   CDC5LはSOX9、COL2A1、Wee1のpre-mRNAスプライシングを調整し初期軟骨細胞分化と増殖を促進する  

    日本整形外科学会雑誌  2021.8  (公社)日本整形外科学会

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  • 伊集院 俊郎, 大石 一樹, 俵積田 裕紀, 前田 真吾, 谷口 登   肩関節rotator cuff tear arthropathyのラット・モデル作製と表現型の解析  

    日本骨代謝学会学術集会プログラム抄録集  2022.7  (一社)日本骨代謝学会

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  • 井内 智洋, 伊集院 俊郎, 俵積田 裕紀, 増田 裕介, 前迫 真吾, 前田 真吾, 谷口 昇   肩腱板断裂関節症モデルではBMPシグナルが活性化する  

    日本骨代謝学会学術集会プログラム抄録集  2023.7  (一社)日本骨代謝学会

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  • 伊集院 俊郎, 井内 智洋, 俵積田 裕紀, 増田 裕介, 前田 真吾, 谷口 昇   肩甲上腕関節の関節包靱帯複合体はcuff tear arthropathyの進展防止機構である  

    日本整形外科学会雑誌  2023.8  (公社)日本整形外科学会

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  • 俵積田 裕紀, 冨永 博之, 増田 裕介, 井内 智洋, 河村 一郎, 前田 真吾, 谷口 昇   老化促進マウスSAMP8の骨量は類骨増加を伴い減少する  

    日本整形外科学会雑誌  2024.3  (公社)日本整形外科学会

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  • 井内 智洋, 伊集院 俊郎, 俵積田 裕紀, 増田 裕介, 前迫 真吾, 前田 真吾, 谷口 昇   新規肩腱板断裂関節症モデルにおけるBMPシグナルの活性化  

    日本整形外科学会雑誌  2023.8  (公社)日本整形外科学会

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  • 井内 智洋, 伊集院 俊郎, 増田 裕介, 俵積田 裕紀, 前田 真吾, 谷口 昇   改良型腱板断裂性肩関節症モデルにおけるBMPシグナル活性  

    日本整形外科学会雑誌  2024.3  (公社)日本整形外科学会

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  • 八尋 雄平, 前田 真吾, 伊集院 俊郎, 俵積田 裕紀, 谷口 昇   分子生物学研究の最前線 BMP標的遺伝子であるAtoh8の骨代謝における役割  

    日本整形外科学会雑誌  2022.9  (公社)日本整形外科学会

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  • 伊集院 俊郎, 大石 一樹, 俵積田 裕紀, 前田 真吾, 谷口 昇   ラット肩腱板インピンジメントtendinopathyモデルにおける腱板の組織学的・機械的特性とHmgb1発現  

    日本整形外科学会雑誌  2022.3  (公社)日本整形外科学会

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  • 伊集院 俊郎, 大石 一樹, 俵積田 裕紀, 前田 真吾, 谷口 昇   ラット肩インピンジメントモデル樹立と腱板tendinopathyの分子生物学的評価  

    移植  2022.2  (一社)日本移植学会

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  • 伊集院 俊郎, 大石 一樹, 俵積田 裕紀, 前田 真吾, 谷口 昇   ラットrotator cuff tear arthropathyモデルの確立と表現型の解析  

    日本整形外科学会雑誌  2022.9  (公社)日本整形外科学会

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  • 増田 裕介, 俵積田 裕紀, 井内 智洋, 伊集院 俊郎, 冨永 博之, 前田 真吾, 谷口 昇   マウスの本態性と二次性サルコペニアに共通して発現変動する新規マイオカインの同定  

    日本整形外科学会雑誌  2023.8  (公社)日本整形外科学会

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  • 俵積田 裕紀, 冨永 博之, 増田 裕介, 井内 智洋, 前田 真吾, 谷口 昇   マウスにおける本態性と2次性サルコペニアに共通する新規マイオカインの検索  

    移植  2023.12  (一社)日本移植学会

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  • 増田 裕介, 俵積田 裕紀, 井内 智洋, 伊集院 俊郎, 前田 真吾, 谷口 昇   マウスにおける本態性と2次性サルコペニアに共通する新規マイオカインの検索  

    日本骨代謝学会学術集会プログラム抄録集  2023.7  (一社)日本骨代謝学会

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  • 俵積田 裕紀, 増田 裕介, 冨永 博之, 河村 一郎, 前田 真吾, 谷口 昇   オステオサルコペニアに関連する新たなマイオカインの検索  

    Journal of Spine Research  2023.4  (一社)日本脊椎脊髄病学会

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  • 俵積田 裕紀, 前田 真吾, 伊集院 俊郎, 谷口 昇   オステオサルコペニアに関わる新規マイオカインの検索  

    日本骨代謝学会学術集会プログラム抄録集  2022.7  (一社)日本骨代謝学会

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  • 立花 直寛, 千々松 良太, 岡田 寛之, 谷口 優樹, 尾市 健, 土肥 透, 矢野 文子, 前田 真吾, 田中 栄, 齋藤 琢   scRNA-seqを用いた頸椎後縦靱帯骨化症の発症における疾患感受性遺伝子RSPO2の役割の検証  

    日本骨代謝学会学術集会プログラム抄録集  2021.10  (一社)日本骨代謝学会

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  • 俵積田 裕紀, 前田 真吾, 伊集院 俊郎, 谷口 昇   SAMP8老化促進マウスのオステオサルコペニア・モデルとしての可能性  

    日本整形外科学会雑誌  2022.9  (公社)日本整形外科学会

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  • 立花 直寛, 千々松 良太, 岡田 寛之, 尾市 健, 谷口 優樹, 中元 秀樹, 加藤 壯, 土肥 透, 松林 嘉孝, 大島 寧, 矢野 文子, 前田 真吾, 田中 栄, 齋藤 琢   Rspo2/Prg4陽性細胞は異所性軟骨内骨化を抑制して腱・靱帯の恒常性に寄与する  

    Journal of Spine Research  2022.3  (一社)日本脊椎脊髄病学会

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  • 俵積田 裕紀, 大石 一樹, 伊集院 俊郎, 冨永 博之, 前田 真吾, 谷口 昇   2つのサルコペニア・マウスモデルにおいて筋萎縮マーカー(Irisin、Atrogin1、Murf1)の発現は筋萎縮と必ずしも相関しない  

    日本整形外科学会雑誌  2022.3  (公社)日本整形外科学会

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  • 俵積田 裕紀, 増田 裕介, 井内 智洋, 伊集院 俊郎, 前田 真吾, 谷口 昇   高齢SAMP8は骨軟化症様骨量減少を呈する  

    日本骨代謝学会学術集会プログラム抄録集  2023.7  (一社)日本骨代謝学会

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  • 俵積田 裕紀, 冨永 博之, 増田 裕介, 井内 智洋, 伊集院 俊郎, 河村 一郎, 前田 真吾, 谷口 昇   高齢SAMP8はMGP発現増加を伴う骨軟化症様骨量減少を呈する  

    日本整形外科学会雑誌  2023.8  (公社)日本整形外科学会

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Awards

  • 奨励賞

    日本整形外科学会  

  • 学会賞

    日本軟骨代謝学会  

Research Projects

  • HMGB1とHMGB2の骨リモデリングにおける機能解析~炎症加齢と骨粗鬆症~

    Grant number:22K09309  2022.4 - 2025.3

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    谷口 昇, 前田 真吾

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    Grant amount:\4160000 ( Direct Cost: \3200000 、 Indirect Cost:\960000 )

  • 新規サルコペニア関連マイオカインとオステオカインの検索

    Grant number:22K09336  2022.4 - 2025.3

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    冨永 博之, 谷口 昇, 前田 真吾

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    Grant amount:\3900000 ( Direct Cost: \3000000 、 Indirect Cost:\900000 )

  • メラトニン欠乏に起因した側弯症の病態解明:原因候補遺伝子Tbx1との機能解析

    Grant number:21K09303  2021.4 - 2024.3

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    河村 一郎, 前田 真吾, 谷口 昇

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    Grant amount:\3900000 ( Direct Cost: \3000000 、 Indirect Cost:\900000 )

    メラトニンと脊柱側弯症の関連は報告されており、まず下流の経路で側弯に至る機序を解明すべく、本邦における大規模ゲノムワイド関連解析で候補となったTbx1遺伝子の関連を確認した。側弯症の原因器官も明らかではないため、骨芽細胞モデルとしてST-2細胞、MC3T3E1細胞、軟骨モデルとしてATDC5細胞を筋モデルとしてC2C12細胞を用い、それぞれの分化における発現変動を確認したが、変化が微弱な事から、Tbx1の役割は限定的であると判断した。
    脳質のReisssner’s fiberに存在するSCO-spondin(Sspo)と側弯形成、松果体とSspoの関係、SspoとUTS2Rとの関連はそれぞれ報告されているが、どのような機序で側弯を形成させているかは不明である。そこでUTS2Rの機能解析を進める事にした。内因性UTS2Rの発現をST-2、MC3T3E1、ATDC5、C2C12及びMSCを用い、それぞれの分化おけるUTS2Rの挙動を確認すると、C2C12とMSCの分化とともに変化した。UTS2R のリガンドであるUrotensinおよびUTS2Rの阻害剤、そしてUts2r siRNAを用い、その分化表現型をReal time PCRと免疫染色を用いて確認した。阻害剤暴露によりMyf1とMyf7はともに抑制され、siUts2rを用いたloss of function実験でもMyf1とMyf7はともに抑制された。問題点として筋分化のどの時点で影響しているかが判明しておらず、その表現型や再現性を確立している。In vitroにおけるUTS2Rの関与が確認し、KOマウスを入手して表現型を確認する予定である。
    筋分化における側弯形成の標的組織として筋が関与していることが示唆され、松果体―Sspo ―UTS2R を介したメカニズムにより筋原性に側弯症が引き起こされる可能性が示唆された。

  • Functional analysis of Sox9/Scx-target genes for regenration of shoulder rotator cuff enthesis

    Grant number:20K09482  2020.4 - 2023.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

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    Grant amount:\4290000 ( Direct Cost: \3300000 、 Indirect Cost:\990000 )

  • シングルセル解析技術に立脚した傍脊柱靱帯の構成細胞解析と後縦靭帯骨化症の病態解明

    Grant number:20K09495  2020.4 - 2023.3

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    大島 寧, 齋藤 琢, 前田 真吾, 谷口 優樹

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    Grant amount:\4290000 ( Direct Cost: \3300000 、 Indirect Cost:\990000 )

    後縦靭帯骨化症(OPLL)は進行性の後縦靭帯の骨化により脊髄が圧迫される原因不明の難病であり、本邦の有病率は約3%と比較的頻度が高い。頚椎OPLLのゲノムワイド関連解析(GWAS)によって疾患感受性候補遺伝子の1つとしてRSPO2が同定され、当研究室はその機能解析を担当してきた。その中で、RSPO2はWNTシグナルを介して骨・軟骨分化を制御するだけでなく、靭帯組織周辺の組織幹細胞で強く発現し、stemnessの維持に関与している可能性を見出した。本研究ではシングルセル解析を駆使してヒト傍脊柱靭帯を構成する細胞の種類と比率を調べ、OPLL患者の靱帯に特有の細胞の動態を解明するとともに、RSPO2とその受容体を発現する細胞の種類を検証する。それらを踏まえ、RSPO2が靱帯構成細胞に及ぼす作用を細胞種ごとにin vitroで解析した上で、マウス腱骨化モデルを用いてin vivoで統合的に検証してきた。2021年度は独自のマウス腱骨化モデルにおけるシングルセル解析に加え、RSPO2を発現する細胞のトラッキングを行い、このプロジェニターがどのような挙動を示すのかを追跡した。また公共データベースにデポジットされているマウス腱障害モデルのシングルセル解析のデータも用いて比較解析を行い、RSPO2陽性のサブセットがどのような性質を有するかについて広く解析を行った。手術サンプルからヒト靭帯細胞を単離し、様々な分化系においてRSPO2の機能解析も行い、異所性軟骨内骨化における方向性を検討した。

  • Analysis of the function of CTNNBL1 in osteoblast differentiation

    Grant number:18K09111  2018.4 - 2021.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

    Kawamura Ichiro

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    Grant amount:\4420000 ( Direct Cost: \3400000 、 Indirect Cost:\1020000 )

    We initially analyzed the function of CTNNBL1 in osteochondrogenic differentiation, but the phenotype was not reproducible, so we proceeded to analyze the function of its binding partner CDC5L. In a series of analyses, CDC5L was found to promote early chondrogenic differentiation and inhibit osteoblast differentiation. In addition, CDC5L may inhibit the differentiation of undifferentiated mesenchymal cells into tendons and ligaments. These results suggest that CDC5L may be a molecular switch from osteochondral progenitor cells to chondrocyte differentiation. It was suggested that it may play an important role in the initial ligamentous cartilage degeneration during the ossification process, or in the chondrocyte differentiation of interstitial and vascular cells.

  • Functional analysis of CDC5L as a candidate causal gene for ossification of the posterior lingitudinal ligamant of the spine

    Grant number:17K10933  2017.4 - 2020.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

    Tominaga Hiroyuki

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    Grant amount:\4550000 ( Direct Cost: \3500000 、 Indirect Cost:\1050000 )

    The ossification of the posterior longitudinal ligament (OPLL) of the spine is an intractable disease of unknown origin, which causes severe myelopathy. We have performed a genome-wide association study to identify cell division cycle 5-like (CDC5L) gene in one of the six disease susceptibility regions. We studied its expression profile and function of CDC5L regarding osteochondrogenic differentiation. CDC5L protein was substantially expressed not only in osteoblastic and chondrocytic cells adjacent to PLL ossification area, but also in non-ligament cells such as the stromal fibrous cells in ossified area and the blood vessel cells in the ligament. Loss of Cdc5l by siRNA greatly enhanced the osteoblastic differentiation, whereas chondrogenesis was suppressed. These results suggest Cdc5l to be a molecular switch to prefer chondrogenesis from osteochondro-progenitors. CDC5L was expressed in OPLL tissue in vivo, while it suppressed osteogenesis or promoted early chondrogenesis, in vitro.

  • Functional analysis of STK38L, the OPLL-associated gene, and research of its target genes in endochondral ossification.

    Grant number:16K10910  2016.4 - 2019.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

    Kakoi Hironori, MATSUYAMA Kanehiro, SHINOHARA Naohiro, YAHIRO Yuhei

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    Grant amount:\4680000 ( Direct Cost: \3600000 、 Indirect Cost:\1080000 )

    siRNA knockdown of STK38L in mesenchymal cell lines resulted in inhibition of osteoblast commitment and promotion of chondrocyte differentiation. Expression of STK38L was increased in ATDC5 chondrocyte upon stimulation of differentiation. We performed immunohistochemistry of STK38L on clinical samples of ossification of posterior longitudinal ligament (OPLL) to find the positive signal in chondrocytic cells of degenerated ligament, whereas normal ligament cells showed no signals. The cell growth was inhibited by loss of STK38L. These results suggest that STK38L play a negative role in formation of OPLL by keeping chondrocytic cells in the proliferating state, which should block maturation of chondrocytes into hypertrophic chondrocytes and subsequent ossification process.

  • Identification and functional analysis of candidate causal genes of the ossification of posterior longitudinal ligament of the spine

    Grant number:15K10410  2015.4 - 2018.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

    Kawamura Ichiro

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    Grant amount:\4940000 ( Direct Cost: \3800000 、 Indirect Cost:\1140000 )

    We tried to isolate mRNA from posterior longitudinal ligament of cervical spine of mice, however, we could not because the tissue was too small. We selected candidate causal genes of OPLL in the sensitive genome area identified by GWAS, and performed immunohistochemistry against the coding proteins. All the selected proteins were detected in the degenerated ligament cells in the OPLL specimens.

  • Roles of Atoh8 in differentiation of osteoblasts and adipocytes

    Grant number:15K10486  2015.4 - 2018.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

    MAEDA Shingo

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    Grant amount:\4810000 ( Direct Cost: \3700000 、 Indirect Cost:\1110000 )

    Number and bone-forming activity of osteoblasts in bone marrow decreases in aging bone, which leads to osteoporosis. However, the mechanism is not fully understood. We analyzed function of Atoh8, a novel direct target gene of canonical bone morphogenetic protein (BMP) signaling, in osteoblasts in vivo and in vitro.siRNA-mediated loss of Atoh8 promoted osteoblast differentiation, however, bone formation parameters were not altered in Atoh8 knockout (KO) mice, assessed by micro-CT and bone morphohistometry analysis.Instead, osteoclast number and bone resorption was increased in KO mice bone, and bone volume was significantly reduced.Rankl/Opg expression ratio in KO osteoblast was increased which enhanced differentiation of osteoclasts.

  • 骨髄脂肪化原因候補遺伝子Atoh8の骨芽細胞・脂肪細胞分化選別における機能解析

    2015 - 2017

    日本学術振興会  基盤研究(C) 

    前田 真吾

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  • Molecular mechanism of osteoblast differentiation.

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