MicroRNA-584-5p/RUNX family transcription factor 2 axis mediates hypoxia-induced osteogenic differentiation of periosteal stem cells  

作　　者：Jia-Jia Lu Xiao-Jian Shi Qiang Fu Yong-Chuan Li Lei Zhu Nan Lu 

机构地区：[1]Department of Orthopedic Trauma Surgery,Shanghai Fourth People’s Hospital,School of Medicine,Tongji University,Shanghai 200001,China [2]Department of Orthopedic Trauma Surgery,Shanghai Changzheng Hospital,Shanghai 200001,China [3]Department of Orthopedic Trauma,Haimen People’s Hospital of Jiangsu Province,Nantong 226100,Jiangsu Province,China

出　　处：《World Journal of Stem Cells》2023年第10期979-988,共10页世界干细胞杂志（英文版）（电子版）

基　　金：Supported by Sailing Program of Naval Medical University,Program of Shanghai Hongkou District Health Commission,No.2202-27;Special Funds for Activating Scientific Research of Shanghai Fourth People’s Hospital,No.sykyqd05801.

摘　　要：BACKGROUND The hypoxic environment during bone healing is important in regulating the differentiation of periosteal stem cells(PSCs)into osteoblasts or chondrocytes;however,the underlying mechanisms remain unclear.AIM To determine the effect of hypoxia on PSCs,and the expression of microRNA-584-5p(miR-584-5p)and RUNX family transcription factor 2(RUNX2)in PSCs was modulated to explore the impact of the miR-584-5p/RUNX2 axis on hypoxiainduced osteogenic differentiation of PSCs.METHODS In this study,we isolated primary mouse PSCs and stimulated them with hypoxia,and the characteristics and functional genes related to PSC osteogenic differentiation were assessed.Constructs expressing miR-584-5p and RUNX2 were established to determine PSC osteogenic differentiation.RESULTS Hypoxic stimulation induced PSC osteogenic differentiation and significantly increased calcified nodules,intracellular calcium ion levels,and alkaline phosphatase(ALP)activity in PSCs.Osteogenic differentiation-related factors such as RUNX2,bone morphogenetic protein 2,hypoxia-inducible factor 1-alpha,and ALP were upregulated;in contrast,miR-584-5p was downregulated in these cells.Furthermore,upregulation of miR-584-5p significantly inhibited RUNX2 expression and hypoxia-induced PSC osteogenic differentiation.RUNX2 was the target gene of miR-584-5p,antagonizing miR-584-5p inhibition in hypoxia-induced PSC osteogenic differentiation.CONCLUSION Our study showed that the interaction of miR-584-5p and RUNX2 could mediate PSC osteogenic differentiation induced by hypoxia.

关 键 词：Periosteal stem cell Osteogenic differentiation RUNX family transcription factor 2 MiroRNA-584-5p 

分 类 号：R739.41[医药卫生—肿瘤]