摘要Human bone marrow mesenchymal stem cells(hBMMSCs)are a promising cell source for bone engineering owing to their high potential to differentiate into osteoblasts.The objective of the present study is to assess microRNA-126(miR-126)and examine its effects on the osteogenic differentiation of hBMMSCs.In this study,we investigate the role of miR-126 in the progression of osteogenic differentiation(OD)as well as the apoptosis and inflammation of hBMMSCs during OD induction.OD is induced in hBMMSCs,and matrix mineralization along with other OD-associated markers are evaluated by Alizarin Red S(AR)staining and quantitative PCR(qPCR).Gain-and loss-of-function studies are performed to demonstrate the role of miR-126 in the OD of hBMMSCs.Flow cytometry and qPCR-based cytokine expression studies are performed to investigate the effect of miR-126 on the apoptosis and inflammation of hBMMSCs.The results indicate that miR-126 expression is downregulated during the OD of hBMMSCs.Gain-and loss-of function assays reveal that miR-126 upregulation inhibits the differentiation of hBMMSCs into osteoblasts,whereas the downregulation of miR-126 promotes hBMMSC differentiation,as as-sessed by the determination of osteogenic genes and alkaline phosphatase activity.Furthermore,the miR-126 level is positively correlated with the production of inflammatory cytokines and apoptotic cell death.Additionally,our results suggest that miR-126 negatively regulates not only B-cell lymphoma 2(Bcl-2)expression but also the phosphorylation of extracellular signal-regulated protein kinase(ERK)1/2.Moreover,restoring ERK1/2 activity and upregulating Bcl-2 expression counteract the miR-126-mediated suppression of OD in hBMMSCs by promoting inflammation and apoptosis,respectively.Overall,our findings suggest a novel molecular mechanism relevant to the differentiation of hBMMSCs into osteoblasts,which can potentially facilitate bone formation by counteracting miR-126-mediated suppression of ERK1/2 activity and Bcl-2 expression.