鹿児島大学 · 医歯学総合研究科

研究关键词platelet-derived growth factor BB・CD10-positive cells・osteogenic differentiation・adipogenic differentiation・mesenchymal stem cells・reactive oxygen species・polymethoxyflavones・lymphangiogenesis

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• Oura Y., Ishii M., Miyata H., Ikeda N., Sakurai T., Suehiro F., Komabashiri N., Nishimura M. . Evaluation of the effect of platelet-derived growth factor-BB on the biological activity of human2025 · 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 Scopus PubMed
• Sakurai T., Ishii M., Miyata H., Ikeda N., Suehiro F., Komabashiri N., Oura Y., Nishimura M. . Effect of CD10-positive cells on osteogenic differentiation of human maxillary/mandibular bone ma2024 · 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 Scopus PubMed
• 櫻井 智章, 小野 草太, 宮田 春香, 駒走 尚大, 松本 哲彦, 益崎 与泰, 末廣 史雄, 嶺崎 良人, 石畑 清秀, 中村 梢, 西村 正宏2022 · 記述言語： 日本語 出版者・発行元： 南九州歯学会
• Miyata H., Ishii M., Suehiro F., Komabashiri N., Ikeda N., Sakurai T., Nishimura M. . Elucidation of adipogenic differentiation regulatory mechanism in human maxillary/mandibular bone marrow-d2022 · 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 Scopus PubMed

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