microRNA-23a inhibits osteogenic differentiation of human bone marrow-derived mesenchymal stem cells by targeting LRP5

Abstract

Emerging evidence indicates that microRNAs (miRNA, or miR) play vital roles in regulating osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs). Elucidation of the molecular mechanisms that govern BMSCs osteogenic differentiation is of paramount importance for improving the treatment of bone-related diseases. In our current study, we investigated the role of miR-23a in BMSCs osteogenesis. Our results revealed that miR-23a was significantly downregulated during osteogenic differentiation. Overexpression of miR-23a inhibited osteogenic differentiation of hBMSCs in vitro, whereas downregulation of miR-23a enhanced the process. Target prediction analysis and dual luciferase reporter assays confirmed that low-density lipoprotein (LDL)-receptor-related protein 5 (LRP5) was a direct target of miR-23a. Furthermore, knockdown of LRP5 inhibited osteogenic differentiation of hBMSCs, similar to the effect observed in upregulation miR-23a. Our data indicate that miR-23a plays an inhibitory role in osteogenic differentiation of hBMSCs, which may act by targeting LRP5.

Keywords: Human bone marrow-derived mesenchymal stem cells; LRP5; Osteogenic differentiation; microRNA-23a.