miR-384-5p targets Gli2 and negatively regulates age-related osteogenic differentiation of rat bone marrow mesenchymal stem cells.

Aberrant microRNA (miRNA) expression correlates with age-related osteoporosis, which impairs bone formation by regulating osteoblastic activity, thus leading to age-related bone loss. In this study, we observed that miR-384-5p was significantly upregulated in bone marrow mesenchymal stem cells (BMSCs) from aged rats as compared with BMSCs from young rats. In vitro functional assays revealed that overexpression of miR-384-5p in young BMSCs inhibited osteogenic differentiation and accelerated senescence, whereas a knockdown of miR-384-5p in aged BMSCs had the opposite effects. Furthermore, we demonstrated that miR-384-5p inhibited the expression of Gli2 both at the mRNA and protein levels by directly binding to the 3' untranslated region (3'UTR) of Gli2 mRNA. The osteogenic capacity of Gli2 knockdown BMSCs was rejuvenated by miR-384-5p inhibition. Finally, in vivo assays showed that inhibition of miR-384-5p prevented bone loss and increased the osteogenic capacity in aged rats. Overall, our study suggests that miR-384-5p functions as a negative regulator of osteogenesis, indicating that inhibition of miR-384-5p may be a therapeutic strategy against age-related bone loss.