MiRNA-128-3p induces osteogenic differentiation of bone marrow mesenchymal stem cells via activating the Wnt3a signaling.

Abstract

To clarify the biological function of miRNA-128-3p in influencing the progression of osteoporosis by inducing osteogenic differentiation of MSCs via activating the Wnt3a signaling. Dynamic expression levels of miRNA-128-3p in osteogenically differentiated MSCs at the different time points were detected by qRT-PCR. The binding sites in the seed sequence of miRNA-128-3p and Wnt3a were predicted using the bioinformatic tool, and their interaction was further confirmed by Dual-Luciferase reporter assay. Co-regulation of miRNA-128-3p and Wnt3a on relative levels of osteogenesis-associated genes, ALP activity and mineralization ability in glucocorticoid-induced MSCs were assessed. MiRNA-128-3p was gradually upregulated with the prolongation of osteogenic differentiation of MSCs. Overexpression of miRNA-128-3p reversed the declines in glucocorticoid-induced expression levels of osteogenesis-associated genes (Bglap, RUNX2 and BMP-2), ALP activity and mineralization ability in MSCs. Wnt3a was able to bind miRNA-128-3p. Its level was positively regulated by miRNA-128-3p in MSCs. Enhanced ALP activity and mineralization ability in glucocorticoid-induced MSCs overexpressing Wnt3a were partially abolished by knockdown of miRNA-128-3p. By positively regulating Wnt3a, miRNA-128-3p alleviates the progression of osteoporosis through inducing osteogenic differentiation of MSCs.