BMSC-derived extracellular vesicles promoted osteogenesis via Axin2 inhibition by delivering MiR-16-5p

Osteoporosis (OP) is a systemic bone disease caused by an imbalance in osteogenesis and osteoclastic resorption. Extracellular vesicles (EVs)-encapsulated miRNAs from bone mesenchymal stem cells (BMSCs) have been reported to participate in osteogenesis. MiR-16-5p is one of the miRNAs that regulates osteogenic differentiation; however, studies have shown that its role in osteogenesis is controversial. Thus, this study aims to investigate the role of miR-16-5p from BMSC-derived extracellular vesicles (EVs) in osteogenic differentiation and uncover the underlying mechanisms. In this study, we used an ovariectomized (OVX) mouse model and an H₂O₂-treated BMSCs model to investigate the effects of BMSC-derived EVs and EV-encapsulated miR-16-5p on OP and the underlying mechanisms. Our results proved that the miR-16-5p level was significantly decreased in H₂O₂-treated BMSCs, bone tissues of OVX mice, and lumbar lamina tissues from osteoporotic women. EVs-encapsulated miR-16-5p from BMSCs could promote osteogenic differentiation. Moreover, the miR-16-5p mimics promoted osteogenic differentiation of H₂O₂-treated BMSCs, and the effects exerted by miR-16-5p were mediated by targeting Axin2, a scaffolding protein of GSK3β that negatively regulates the Wnt/β-catenin signaling pathway. This study provides evidence that EVs-encapsulated miR-16-5p from BMSCs could promote osteogenic differentiation by repressing Axin2.