Gravity, a regulation factor in the differentiation of rat bone marrow mesenchymal stem cells

Rat BMSCs (rBMSCs) were cultured under hypergravity or simulated microgravity (SMG) conditions with or without inducement medium. The expression levels of the characteristic proteins were measured and analyzed using immunocytochemical, RT-PCR and Western-blot analyses. After treatment with 5-azacytidine and hypergravity, rBMSCs expressed more characteristic proteins of cardiomyocytes such as cTnT, GATA4 and β-MHC; however, fewer such proteins were seen with SMG. After treating rBMSCs with osteogenic inducer and hypergravity, there were marked increases in the expression levels of ColIA1, Cbfa1 and ALP. Reverse results were obtained with SMG. rBMSCs treated with adipogenic inducer and SMG expressed greater levels of PPARgamma. Greater levels of Cbfa1- or cTnT-positive cells were observed under hypergravity without inducer, as shown by FACS analysis. These results indicate that hypergravity induces differentiation of rBMSCs into force-sensitive cells (cardiomyocytes and osteoblasts), whereas SMG induces force-insensitive cells (adipocytes).Taken together, we conclude that gravity is an important factor affecting the differentiation of rBMSCs; this provides a new avenue for mechanistic studies of stem cell differentiation and a new approach to obtain more committed differentiated or undifferentiated cells.The availability of sufficient, suitable cells is a limiting factor in regenerative medicine or cellular therapy which is a potential method for treatment of some diseases, such as myocardial infarction and bone defects. Mesenchymal stem cells (MSCs) are an attractive source of material for cellular replacement strategies for clinical applications and tissue engineering owing to their ability to replicate in the undifferentiated state, to differentiate into different cell lineages and the low immunogenic response in vivo [1-4]. Many studies have reported that MSCs can differentiate into cardiomyocytes after exposure to 5-azacydine (5-aza) [5,6], into osteoblasts in th