microRNA-576-5p ameliorates dexamethasone-induced BMSC injury by suppressing ANXA2

Dysfunction of Bone Marrow Derived Mesenchymal Stem Cells (BMSCs) induced by glucocorticoids has been identified as a key pathological mechanism of steroid-induced osteonecrosis of the femoral head (SONFH). Consequently, restoring the function of BMSCs is a vital strategy for treating SONFH. This study aimed to investigate the role of microRNA-576-5p (miR-576-5p) and Annexin A2 (ANXA2) in SONFH and dexamethasone (DEX) cultured BMSCs, expecting to seek new therapeutic strategies for SONFH. RNA and protein samples were extracted from the bone tissue of femoral heads and DEX treated BMSCs to verify the potential relationship among miR-576-5p, ANXA2 and SONFH. Then, the interaction between miR-576-5p and ANXA2 mRNA was investigated through dual luciferase reporter assays. Finally, BMSC proliferation, apoptosis, mineralization, and its capacity for pro-osteoclastogenesis after increasing miR-576-5p levels or reducing ANXA2 expression were detected with 10^-5M DEX exposure. The results indicated that miR-576-5p levels were reduced, while ANXA2 protein was upregulated in the femoral heads of SONFH patients and in BMSCs treated with DEX. ANXA2 mRNA is a target gene of miR-576-5p, and overexpression of ANXA2 antagonized the effects of miR-576-5p on BMSCs. Interestingly, both increase of miR-576-5p and knockdown of ANXA2 mitigated the damage of DEX on BMSCs, evidenced by enhanced proliferation and mineralization and reduced apoptosis and pro-osteoclastogenesis capacity. In conclusion, elevating miR-576-5p alleviated DEX-induced BMSC injury by targeting ANXA2 mRNA, which may be a promising treatment option for SONFH.