miR-211-5p/FOXO3 axis accelerates osteogenic differentiation and fracture healing by mediating Wnt/β-catenin pathway

BACKGROUND: As a disease closely related to aging, the prevalence and disability rate of osteoporotic fracture (OPF) are on the rise. MicroRNA (miRNA) expression abnormalities are closely linked to various skeletal disorders, yet the regulatory role of miR-211-5p in OPF remains unclear. OBJECTIVE: To investigate the expression patterns of miR-211-5p in OPF and its molecular mechanisms in the osteogenic differentiation and Wnt/β-catenin pathway of BMSCs and MC3T3-E1 cells. METHODS: Blood samples were collected from patients with osteoporosis (OP) and OPF who were treated in our hospital, as well as from healthy controls (HC). The levels of miR-211-5p and FOXO3 were quantified by RT-qPCR. The functional activity of the cells was evaluated using CCK-8 assay, flow cytometry, and Western blot techniques, respectively. The targeting relationship was verified by dual-luciferase activity reporter assay and RIP assay. RESULTS: Serum miR-211-5p was down-regulated in OPF patients, and holds diagnostic potential for identifying such patients. Following treatment, serum miR-211-5p levels increased over time in OPF patients, and osteogenic induction upregulated miR-211-5p level in BMSCs and MC3T3-E1 cells. miR-211-5p directly targeted FOXO3. Overexpression of FOXO3 partially reversed the activation of miR-211-5p mimic on cell viability, osteogenic markers and Wnt/β-catenin pathway effector markers. CONCLUSION: miR-211-5p promotes bone formation by targeting and inhibiting FOXO3 to activate the Wnt/β-catenin pathway, thereby accelerating fracture healing.