MiR-596 inhibits osteoblastic differentiation and cell proliferation by targeting Smad3 in steroid-induced osteonecrosis of femoral head

Abstract

Background: It is reported that miR-596 has a potential diagnostic value for non-traumatic osteonecrosis of the femoral head (NOFH), but its underlying mechanisms in NOFH is unclear. Methods: The expression of miR-596 and Smad3 was detected by western blot and quantitative real-time PCR. The relationship between the two molecules was explored using Dual-Luciferase Reporter Assay. Glucocorticoid (GC)-dexamethasone, was used to induce bone marrow mesenchymal stem cell (BMSC) osteogenic differentiation, and the effects of miR-596 on BMSC osteogenic differentiation and proliferation were determined. Results: MiR-596 expression was upregulated, while Smad3 expression was inhibited in the bone marrow samples of patients with steroid-induced osteonecrosis of femoral head (SANFH). Overexpression of miR-596 inhibited the proliferation and osteogenic differentiation of BMSCs induced by GC. Meanwhile, the opposite results were observed in the miR-596 inhibitor group. In addition, Smad3 was a target gene of miR-596, and negatively regulated by miR-596. The promotion effect of the miR-596 inhibitor on BMSC proliferation and osteogenic differentiation was reversed by si-Smad3. Conclusion: MiR-596 can suppress GC-BMSC osteoblastic differentiation and proliferation by regulating Smad3 expression.