Promotion Effects of miR-375 on the Osteogenic Differentiation of Human Adipose-Derived Mesenchymal Stem Cells

MicroRNA plays an important role in bone tissue engineering; however, its role and function in osteogenic differentiation warrant further investigation. In this study, we demonstrated that miR-375 was upregulated during the osteogenic differentiation of human adipose-derived mesenchymal stem cells (hASCs). Overexpression of miR-375 significantly enhanced hASCs osteogenesis both in vitro and in vivo, while knockdown of miR-375 inhibited the osteogenic differentiation of hASCs. Mechanistically, microarray analysis revealed DEPTOR as a target of miR-375 in hASCs. Knockdown of DEPTOR accelerated the osteogenic differentiation of hASCs by inhibiting AKT signaling, which mimics miR-375 overexpression. Furthermore, we confirmed that miR-375 regulated osteogenesis by targeting YAP1, and that YAP1 reversely bound to miR-375 promoter to inhibit miR-375 expression. Taken together, our results suggested that miR-375 promoted the osteogenic differentiation of hASCs via the YAP1/DEPTOR/AKT regulatory network, indicating that miR-375-targeted therapy might be a valuable approach to promote bone regeneration. [Display omitted] •miR-375 promotes osteogenic differentiation of hASCs in vitro and in vivo•miR-375 inhibits AKT signaling by directly targeting DEPTOR•YAP1 and miR-375 form a negative feedback loop to regulate hASCs osteogenesis In this article, Zhou and colleagues demonstrate that miR-375 promotes osteogenic differentiation of hASCs both in vitro and in vivo. They revealed that miR-375 inhibits AKT signaling via directly targeting DEPTOR during the osteogenic differentiation of hASCs. Moreover, they found that YAP1 together with miR-375 forms a negative feedback loop to regulate hASCs osteogenesis.