Inhibition of circulating miR-194-5p reverses osteoporosis through Wnt5a/β-catenin signaling-dependent induction of osteogenic differentiation

Abstract Mesenchymal stem cells (MSCs) critically contribute to bone formation and proper induction of osteogenic differentiation can lead to an increase in bone mass. In the present study, we reported that increased miR-194-5p level in plasma is inversely related to the degree of bone formation in osteoporosis patients. We also noted that increased miR-194-5p in the MSCs of ovariectomized (OVX) mice, and agomiR-194-5p manipulation of miR-194-5p significantly suppressed bone formation, both in aged and OVX mice. Furthermore, our in vitro study showed that overexpression of miR-194-5p suppresses osteogenic differentiation, as evidenced by the decreased bone formation marker genes and matrix mineralization. The luciferase assay indicated that wnt5a is a target gene of miR-194-5p that positively regulates osteogenic differentiation. Collectively, these data indicated that miR-194-5p inhibition may be a potential strategy for osteoporosis prevention.