STMN2 promotes osteogenic differentiation and bone formation in mouse bone marrow mesenchymal stem cells via the Wnt signaling pathway

Abstract Stathmin 2 (STMN2) is a microtubule-associated protein whose role in the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) remains unclear. This study aimed to investigate the regulatory role of STMN2 in osteogenic differentiation and bone regeneration in mouse BMSCs. BMSCs were transduced with lentiviral constructs for STMN2 overexpression, STMN2 knockdown, or negative control. Proliferation, migration, ALP activity, mineralization, and expression of RUNX2, BMP2, BGLAP, and COL1A2 were assessed. Transduced BMSCs were implanted into calvarial defects and evaluated by micro-CT, H&E staining, and immunohistochemistry; transcriptome sequencing and Wnt/β-catenin agonist rescue experiments were also performed. STMN2 was upregulated during osteogenesis. Overexpression promoted proliferation, migration, osteogenic differentiation, and in vivo bone formation, whereas knockdown attenuated these effects. A Wnt agonist partially rescued the osteogenic defect in STMN2-knockdown BMSCs. In conclusion, STMN2 promotes the osteogenic differentiation of mouse BMSCs and enhances bone regeneration, identifying it as a potential therapeutic target.