miRNA-223-5p Inhibits Hypoxia-induced Apoptosis of BMSCs and Promotes Repair in Legg-Calvé-Perthes Disease rabbit model by Targeting CHAC2 and Activating the Wnt/β-catenin Signaling Pathway
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Legg-Calvé-Perthes disease (LCPD) involves femoral head osteonecrosis due to disrupted blood supply, leading to joint deformity and early osteoarthritis. This study examines the role of miRNA-223-5p in regulating hypoxia-induced apoptosis and promoting osteogenesis in bone marrow mesenchymal stem cells (BMSCs). Using a juvenile New Zealand white rabbit model of LCPD created through femoral neck ligation, we transfected BMSCs with miR-223-5p mimics, inhibitors, and controls, followed by hypoxic exposure. We assessed the impact of miR-223-5p on BMSC apoptosis using qPCR, Western blotting, and dual-luciferase reporter assays, focusing on the Wnt/β-catenin signaling pathway. In vivo, we evaluated the effects of transplanting miR-223-5p-overexpressing BMSCs into the LCPD model. Our findings indicate that miR-223-5p is downregulated under hypoxic conditions. Overexpression of miR-223-5p in BMSCs inhibited hypoxia-induced apoptosis and activated the Wnt/β-catenin pathway through direct targeting of CHAC2. In vivo, miR-223-5p-overexpressing BMSCs enhanced femoral head osteogenesis and reduced necrosis in the LCPD model. These results suggest that miR-223-5p inhibits hypoxia-induced apoptosis in BMSCs by targeting CHAC2 and activating the Wnt/β-catenin pathway, proposing miR-223-5p as a promising target for improving bone repair in ischemic conditions.
