Duration of simulated microgravity affects the differentiation of mesenchymal stem cells

Previous evidence has suggested that physical microenvironments and mechanical stresses, independent of soluble factors, influence mesenchymal stem cell (MSC) fate. In the present study, simulated microgravity (SMG) was demonstrated to regulate the differentiation of mesenchymal stem cells. This may be a novel strategy for tissue engineering and regenerative medicine. Rat MSCs were cultured for 72 h or 10 days in either normal gravity or a clinostat to model microgravity, followed with culture in diverse differential media. A short period of stimulation (72 h) promoted MSCs to undergo endothelial, neuronal and adipogenic differentiation. In comparison, extended microgravity (10 days) promoted MSCs to differentiate into osteoblasts. A short period of exposure to SMG significantly decreased ras homolog family member A (RhoA) activity. However, RhoA activity significantly increased following prolonged exposure to SMG. When RhoA activity was inhibited, the effects of prolonged exposure to SMG were reversed. These results demonstrated that the duration of SMG regulates the differentiation fate of MSCs via the RhoA-associated pathway.