SIRT1 Regulates Osteogenic Differentiation of BMSCs and H-type Vessels Formation to Promote Healing of Osteoporotic Bone Defects
Objective:To investigate the role of silent information regulator 1(SIRT1)on H-type vessels regenera-tion and bone defect healing in senile osteoporotic state by regulating osteogenic differentiation of bone marrow mesenchymal stem cells(BMSCs)and to explore its specific molecular mechanism.Methods:Immunohistochemical staining was used to detect age-related changes in SIRT1 expression in mouse bone tissue.BMSCs were treated with SIRT1 activator SRT1720 and inhibitor EX527,and the changes in the expression of osteogenic markers and H-type angiogenic factors were detected by RT-qPCR and Western Blot,and the changes in the Wnt/β-catenin signaling pathway in the above process were detected by immunofluorescence staining and Western Blot.A model of osteopo-rotic bone defects was constructed in the elderly,and SRT1720 and EX527 were administered with XAV939,an inhibitor of Wnt signaling pathway,and CHIR-99021,an activator of Wnt signaling pathway,respectively.The differences in the formation of new bone and H-vessel content of the defects were detected by Micro-CT,HE/Mas-son staining,and immunofluorescent staining in the respec-tive groups.Results:The expression of SIRT1 showed an age-increasing down-regulation trend in mouse bone tissues.SIRT1 was able to promote the expression of alkaline phosphatase(ALP),Runt-related transcription factor 2(RUNX2),and the pro-H-type angiogenic factors slit homolog 3(SLIT3)and vascular endothelial growth factor(VEGF),and able to promote the H-type angiogenesis and bone regeneration in the region of osteoporotic bone defects in old age,which was mediated by the Wnt/β-cate-nin signaling pathway.Conclusion:SIRT1 can promote the osteogenic differentiation and H-type angiogenesis of BMSCs by regulating the Wnt/β-catenin signaling pathway,which in turn promotes the healing of bone defects in the osteoporotic state of aged mice.
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