MiR-223-3p Promotes Osteoporosis Progression by Repressing Osteogenic Differentiation via Targeting FHL1/Wnt/β-catenin Signaling

The aim of this research was to unveil the potential along with potential mechanism of miR-223-3p in osteoporosis. RT-qPCR together with western blot was implemented to examine miR-223-3p, FHL1, along with osteogenic markers levels during bone marrow mesenchymal stem cells (BMSCs) differentiation. The ALP activity staining along with alizarin red staining (ARS) were implemented to assess ALP activity as well as the mineralization ability of BMSCs. Binding sequences for miR-223-3p and FHL1 from starBase website were validated through dual-luciferase reporter gene assay. MiR-223-3p was down-regulated in BMSCs during osteoblasts differentiation, and miR-223-3p elevation hindered BMSCs' osteogenic differentiation. FHL1 belonged to the target mRNA of miR-223-3p. FHL1 presented up-regulation in BMSCs during osteoblasts differentiation. More importantly, FHL1 expression was negative modulated by miR-223-3p in BMSCs during osteoblasts differentiation, and FHL1 elevation could inverse the inhibited BMSCs' osteogenic differentiation modulated by miR-223-3p elevation. Furthermore, miR-223-3p elevation repressed the Wnt/β-catenin pathway activity in lithium chloride-treated BMSCs, and FHL1 overexpression counteracted the inhibitory effect of the Wnt/β-catenin pathway caused by miR-223-3p up-regulation. Collectively, miR-223-3p accelerates osteoporosis progression by repressing osteogenic differentiation through targeting FHL1/Wnt/β-catenin signaling.