記述言語：日本語   出版者・発行元：Archives of Oral Biology  

Objective: This study aimed to investigate the effects of platelet-derived growth factor-BB (PDGF-BB) on the biological activities of human mandibular bone marrow-derived mesenchymal stem cells (MBMSCs). Design: PDGF-BB (20 ng/mL) was used to treat MBMSCs, and its effects on their proliferation, osteogenic differentiation, and migration were evaluated. Cell proliferation was evaluated using a WST-1 assay. Osteogenic differentiation was evaluated by measuring the mineralization potential and alkaline phosphatase activity. Cell migration was evaluated using wound healing and Transwell chamber assays. Cytoskeletal reorganization and adhesion dynamics were evaluated using immunofluorescence staining. Changes in intracellular signaling in MBMSCs induced by PDGF-BB stimulation were evaluated using western blotting. Furthermore, we investigated Girdin signaling as the molecular mechanisms underlying the regulation of PDGF-BB-induced cell migration. Results: PDGF-BB treatment did not affect the proliferation or osteogenic differentiation of MBMSCs. PDGF-BB promoted the migration of MBMSCs. PDGF-BB treatment enhanced F-actin filament formation and paxillin localization at the leading edge of cells. PDGF-BB treatment activated Akt signaling in MBMSCs, and the inhibition of Akt signaling effectively suppressed PDGF-BB-induced Akt activation and migration. PDGF-BB promoted the phosphorylation of Girdin in MBMSCs, and the inhibition of Akt signaling attenuated PDGF-BB-induced Girdin activation. Conclusion: This study demonstrated that PDGF-BB strongly induces the migration of MBMSCs without affecting their proliferation or osteogenic differentiation. Furthermore, PDGF-BB-induced migration of MBMSCs may be mediated through the Akt/Girdin signaling pathway. These findings provide important insight into the molecular mechanisms underlying PDGF-BB-induced periodontal tissue regeneration.

DOI： 10.1016/j.archoralbio.2025.106244

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PubMed

記述言語：日本語   出版者・発行元：Archives of Oral Biology  

Objective: This study was aimed at investigating the effect of CD10-positive cells within the maxillary/mandibular bone marrow-derived mesenchymal stem cells (MBMSCs) on osteogenic differentiation of MBMSCs. Design: CD10 expression in iliac bone marrow-derived MSCs (IBMSCs), MBMSCs, and gingival fibroblasts was measured using flow cytometry. The osteogenic potential of 19 MBMSC lines was evaluated, and based on it, they were classified into osteogenic-High and osteogenic-Low groups. The percentage of CD10-positive cells in each group was compared. Effect of coculturing gingival fibroblasts and CD10-positive cells on the osteogenic potential of MBMSCs was also assessed. Expression of tissue inhibitor of metalloprotease-1 (TIMP-1) in osteogenic-High and osteogenic-Low MBMSCs was measured using quantitative real-time polymerase chain reaction, western blotting, and enzyme-linked immunosorbent assay. The molecular mechanisms underlying the regulation of osteogenic differentiation in MBMSCs were investigated. Results: CD10 was not expressed in IBMSCs, but was highly expressed in fibroblasts. In MBMSCs, the CD10-positivity rate varied considerably between cells. MBMSCs with a high-CD10 positivity rate showed low osteogenic potential. Coculture with fibroblasts or CD10-positive cells reduced the osteogenic potential of MBMSCs. TIMP-1 was highly expressed in CD10-positive cells, and osteogenic-Low MBMSCs showed significantly higher TIMP-1 expression compared with osteogenic-High MBMSCs. β-catenin signaling was suppressed in osteogenic-Low MBMSCs. Conclusion: This study revealed that TIMP-1 secreted from CD10-positive cells may be involved in the suppression of the osteogenic potential of MBMSCs by contamination with CD10-positive cells. This finding provides important insights for developing bone regeneration therapies using MBMSCs.

DOI： 10.1016/j.archoralbio.2024.106135

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PubMed

記述言語：日本語   出版者・発行元：Molecular Biology Reports  

Background: Kaempferia parviflora Wall. ex. Baker (KP) has been reported to exhibit anti-obesity effects. However, the detailed mechanism of the anti-obesity effect of KP extract (KPE) is yet to be clarified. Here, we investigated the effect of KPE and its component polymethoxyflavones (PMFs) on the adipogenic differentiation of human mesenchymal stem cells (MSCs). Methods and results: KPE and PMFs fraction (2.5 µg/mL) significantly inhibited lipid and triacylglyceride accumulation in MSCs; lipid accumulation in MSCs was suppressed during the early stages of differentiation (days 0–3) but not during the mid (days 3–7) or late (days 7–14) stages. Treatment with KPE and PMFs fractions significantly suppressed peroxisome proliferator-activated receptor-γ (PPARγ), CCAAT/enhancer binding protein α (C/EBPα), and various adipogenic metabolic factors. Treatment with KPE and PMFs fraction induced the activation of AMP-activated protein kinase (AMPK) signaling, and pretreatment with an AMPK signaling inhibitor significantly attenuated KPE- and PMFs fraction-induced suppression of lipid formation. Conclusions: Our findings demonstrate that KPE and PMFs fraction inhibit lipid formation by inhibiting the differentiation of undifferentiated MSCs into adipocyte lineages via AMPK signaling, and this may be the mechanism underlying the anti-obesity effects of KPE and PMFs. Our study lays the foundation for the elucidation of the anti-obesity mechanism of KPE and PMFs.

DOI： 10.1007/s11033-024-09739-4

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PubMed

記述言語：日本語   出版者・発行元：Molecular Biology Reports  

Background: Maxillary/mandibular bone marrow-derived mesenchymal stem cells (MBMSCs) exhibit a unique property of lower adipogenic potential than other bone marrow-derived MSCs. However, the molecular mechanisms regulating the adipogenesis of MBMSCs remain unclear. This study aimed to explore the roles of mitochondrial function and reactive oxygen species (ROS) in regulating the adipogenesis of MBMSCs. Methods and results: MBMSCs exhibited significantly lower lipid droplet formation than iliac BMSCs (IBMSCs). Moreover, the expression levels of CCAAT/enhancer-binding protein β (C/EBPβ), C/EBPδ, and early B cell factor 1 (Ebf-1), which are early adipogenic transcription factors, and those of peroxisome proliferator-activated receptor-γ (PPARγ) and C/EBPα, which are late adipogenic transcription factors, were downregulated in MBMSCs compared to those in IBMSCs. Adipogenic induction increased the mitochondrial membrane potential and mitochondrial biogenesis in MBMSCs and IBMSCs, with no significant difference between the two cell types; however, intracellular ROS production was significantly enhanced only in IBMSCs. Furthermore, NAD(P)H oxidase 4 (NOX4) expression was significantly lower in MBMSCs than in IBMSCs. Increased ROS production in MBMSCs by NOX4 overexpression or treatment with menadione promoted the expression of early adipogenic transcription factors but did not induce that of late adipogenic transcription factors or lipid droplet accumulation. Conclusions: These results suggest that ROS may be partially involved in the process of MBMSC adipogenic differentiation from undifferentiated cells to immature adipocytes. This study provides important insights into the tissue-specific properties of MBMSCs.

DOI： 10.1007/s11033-023-08528-9

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PubMed

記述言語：日本語   出版者・発行元：Archives of Oral Biology  

Objective: This study aims to investigate the underlying molecular mechanisms that regulate the adipogenic differentiation of maxillary/mandibular bone marrow-derived mesenchymal stem cells (MBMSCs). Design: MBMSCs and iliac bone marrow-derived MSCs (IBMSCs) were compared for osteogenic, chondrogenic, and adipogenic differentiation. Cell surface antigen expression was examined using flow cytometry, and stem cell marker expression was assessed using real-time polymerase chain reaction (PCR). Various adipogenic regulatory factors’ expression was evaluated using real-time PCR and western blotting. Results: No significant differences in cell surface antigen profiles or stem cell marker expression in MBMSCs and IBMSCs were observed. MBMSCs and IBMSCs displayed similar osteogenic and chondrogenic potentials, whereas MBMSCs showed significantly lower adipogenic potentials than those shown by IBMSCs. Expression of CCAAT/enhancer binding protein β (C/EBPβ), C/EBPδ, early B-cell factor 1 (Ebf-1), and Krüppel-like factor 5 (KLF5), which are early adipogenic differentiation factors, was suppressed in MBMSCs compared to that in IBMSCs. Peroxisome proliferator-activated receptor-γ (PPARγ) and C/EBPα, which play important roles in the terminal differentiation of adipocytes, was lower in MBMSCs than that in IBMSCs. Furthermore, the level of zinc finger protein 423 (Zfp423), which is involved in the commitment of undifferentiated MSCs to the adipocyte lineage, was significantly lower in MBMSCs than that in IBMSCs. Conclusions: MBMSCs are negatively regulated in the commitment of undifferentiated MSCs to the adipocyte lineage (preadipocytes) as well as in the terminal differentiation of preadipocytes into mature adipocytes. These results may elucidate the site-specific characteristics of MBMSCs.

DOI： 10.1016/j.archoralbio.2022.105608

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PubMed

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語