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...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.展开更多
Bone marrow mesenchymal stem cells(BMSCs),periosteal stem cells(PSCs),and other bone stem cells originate from embryonic bone formation,but their function and stem cell characteristics such as proliferation ability an...Bone marrow mesenchymal stem cells(BMSCs),periosteal stem cells(PSCs),and other bone stem cells originate from embryonic bone formation,but their function and stem cell characteristics such as proliferation ability and differentiation ability change at different anatomical locations.Perichondral-derived stem cells(PCSCs)are more closely related to PSCs in origin and function,usually used to be studied together with PSCs as one type of stem cell.However,this leads to the ignoration of the PCSCs'characteristics.Since the anatomical locations of these two types of stem cells diverse,PCSCs should have some differences from PSCs.In this study,the PCSCs in the perichondrium surrounding the growth plate cartilage expressed CTSK and CD200 same as PSCs.However,when compared the stem cell characteristics of PCSCs with that of PSCs,PCSCs were more elongated than PSCs in morphology and have stronger self-renewal ability,as well as stronger chondrogenic and adipogenic differentiation potentials.This study revealed the stem cell characteristics of PCSCs distinguished from PSCs,which may indicate PCSCs and PSCs should not be treated as one type of cell to research in the future.展开更多
基金Supported by Sailing Program of Naval Medical University,Program of Shanghai Hongkou District Health Commission,No.2202-27Special Funds for Activating Scientific Research of Shanghai Fourth People’s Hospital,No.sykyqd05801.
文摘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.
基金This research was funded by the National Natural Science Foundation of China,grants number 11972068 and 12002026funded by the China Space Station Engineering Experiment Project,grants number HYZHXM01016.
文摘Bone marrow mesenchymal stem cells(BMSCs),periosteal stem cells(PSCs),and other bone stem cells originate from embryonic bone formation,but their function and stem cell characteristics such as proliferation ability and differentiation ability change at different anatomical locations.Perichondral-derived stem cells(PCSCs)are more closely related to PSCs in origin and function,usually used to be studied together with PSCs as one type of stem cell.However,this leads to the ignoration of the PCSCs'characteristics.Since the anatomical locations of these two types of stem cells diverse,PCSCs should have some differences from PSCs.In this study,the PCSCs in the perichondrium surrounding the growth plate cartilage expressed CTSK and CD200 same as PSCs.However,when compared the stem cell characteristics of PCSCs with that of PSCs,PCSCs were more elongated than PSCs in morphology and have stronger self-renewal ability,as well as stronger chondrogenic and adipogenic differentiation potentials.This study revealed the stem cell characteristics of PCSCs distinguished from PSCs,which may indicate PCSCs and PSCs should not be treated as one type of cell to research in the future.