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

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.

Comparison of stem cell characteristics between perichondral-derived stem cells and periosteal stem cells in postnatal rats

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.

2-N,6-O sulfated chitosan evokes periosteal stem cells for bone regeneration

Musculoskeletal injuries and bone defects represent a significant clinical challenge,necessitating innovative approaches for effective bone tissue regeneration.In this study,we investigated the potential of harnessing periosteal stem cells(PSCs)and glycosaminoglycan(GAG)-mimicking materials for in situ bone regeneration.Our findings demonstrated that the introduction of 2-N,6-O sulfated chitosan(26SCS),a GAG-like polysaccharide,enriched PSCs and promoted robust osteogenesis at the defect area.Mechanistically,26SCS amplifies the biological effect of endogenous platelet-derived growth factor-BB(PDGF-BB)through enhancing the interaction between PDGF-BB and its receptor PDGFRβabundantly expressed on PSCs,resulting in strengthened PSC proliferation and osteogenic differentiation.As a result,26SCS effectively improved bone defect repair,even in an osteoporotic mouse model with lowered PDGF-BB level and diminished regenerative potential.Our findings suggested the significant potential of GAG-like biomaterials in regulating PSC behavior,which holds great promise for addressing osteoporotic bone defect repair in future applications.