Stem Cells Dev. 2018 Mar 16. doi: 10.1089/scd.2017.0276. [Epub ahead of print]

miR-450b promotes osteogenic differentiation in vitro and enhances bone formation in vivo by targeting BMP3.

Fan L¹, Fan J², Liu Y³, Li T⁴, Xu H⁵, Yang Y⁶, Deng L⁷, Li H⁸, Zhao RC⁹.

Abstract

Osteoporosis is characterized by deterioration of bone microarchitecture and low bone mass. One of the primary causes of osteoporosis is the decrease in the osteogenic differentiation of mesenchymal stem cells. Tissue engineering therapy with genetically modified mesenchymal stem cells has attracted much attention in the study of bone regeneration. In this study, we found that the expression level of miR-450b was upregulated during osteogenic differentiation of human adipose-derived mesenchymal stem cells (hADSCs). To explore the effect of miR-450b on the osteogenesis of hADSCs, we performed a series of gain- and loss-of-function analyses and demonstrated that miR-450b not only promoted the process of hADSC differentiation to osteoblasts in vitro but also enhanced ectopic bone formation in vivo. Bone morphogenetic protein 3 (BMP3), the most abundant BMP member in bone, was identified as a direct target of miR-450b. Downregulation of the endogenous expression of BMP3 could mimic the effect of miR-450b upregulation on the osteogenic differentiation of hADSCs. Overall, our study first demonstrated that a novel miRNA miR-450b was essential for hADSC differentiation, which could promote osteogenic differentiation in vitro and enhance bone formation in vivo by directly suppressing BMP3.