Abstract
Exposure to microgravity decreases bone volume and increases marrow fat, partly due to impaired BMSC osteogenesis and enhanced adipogenesis. Staphylococcal enterotoxin C2 (SEC2) can influence BMSC differentiation, potentially promoting osteogenesis. This study investigated SEC2's effects on bone loss and marrow fat in hindlimb suspension (HLS) mice and BMSC differentiation under simulated microgravity. Results showed SEC2 alleviated bone deterioration and reduced marrow adiposity, promoting osteogenic over adipogenic differentiation by activating ERK/β-catenin signaling pathways. SEC2 increased ERK phosphorylation and β-catenin nuclear translocation, with effects diminished upon β-catenin knockdown. These findings reveal a novel mechanism by which SEC2 modulates BMSC fate under microgravity, highlighting its potential as a therapeutic agent for preventing bone loss and marrow adiposity in microgravity conditions.