Study On The Inhibitory Effect Of INH-A On Osteogenic Differentiation Of MSCs Induced By BMP9 And The Mechanism

INH-?,a member of TGF-? superfamily,has been involved in bone turnover during the menopausal transition via endocrine effects,and it was previously reported that inhibins may antagonize the function of BMPs.However,one of the most important functions of BMPs is to induce osteogenic differentiation.Also,BMP9 as one of the most potent BMPs to induce osteogenic differentiation has gotten more and more attentions.Nonetheless,the effects of INH-? on osteogenesis remain unknown.Besides,MSCs with the ability to differentiate into multiple mesenchymal lineages,including osteoblasts,adipocyte,chondrocytes and myoblasts in vitro,have become the promising seed cells for bone tissue engineering.Here,we investigated the role of INH-? on BMP9-induced osteogenic differentiation in MSCs and tried to find the mechanism underlying this process.Finally,we found INH-? apparently reduced the classical osteogenic markers and the ectopic bone formation induced by BMP9;and the ratio of OPG to RANKL is obviously declined in the presence of INH-?.In the mechanism,we found that exogenous expression of INH-? inhibits BMP9-induced osteogenic differentiation through blocking BMP/Smad signal transduction and activating NF-?B signal which is repressed by BMP9 in MSCs.Thus,our findings indicated that INH-? has a negative effect on BMP9-induced osteogenic differentiation in MSCs,which may provide a novel insight into the regulation of skeletal development and new strategy for bone tissue engineering.