TGF-β signaling regulates differentiation of MSCs in bone metabolism: disputes among viewpoints

• TGF-β isoforms (β1, β2, β3) exert distinct and sometimes opposing effects on MSC osteogenic differentiation, explaining conflicting literature results. • The review systematically summarizes the molecular mechanisms of TGF-β signaling in bone metabolism, highlighting context-dependent regulation. • Discrepancies in experimental outcomes arise from differences in MSC sources, culture conditions, TGF-β concentrations, and receptor expression. • Understanding TGF-β's dual roles can guide the development of targeted therapies for bone regeneration and treatment of bone diseases.