Inhibin α-subunit inhibits BMP9-induced osteogenic differentiation through blocking BMP/Smad signal and activating NF-κB signal in mesenchymal stem cells

Inhibin-alpha, a member of the transforming growth factor (TGF-beta) 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. Certainly, one of the most important functions of BMPs is to induce osteogenic differentiation. BMP9 as one of the most potent BMPs to induce osteogenic differentiation has gotten more and more attentions. Nonetheless, the effects of inhibin-alpha on osteogenesis remain unknown. Besides, mesenchymal stem cells (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 inhibin-alpha on BMP9-induced osteogenic differentiation in MSCs and tried to discover the mechanism underlying this process. We found inhibin-alpha apparently reduced the classical osteogenic markers and the ectopic bone formation induced by BMP9. In addition, the ratio of OPG to RANKL is declined also in the presence of inhibin-alpha. For mechanism, we found that exogenous expression of inhibin-alpha inhibits BMP9-induced osteogenic differentiation through blocking BMP/Smad signal transduction and activating NF-kappa B signal which is repressed by BMP9. Thus, our findings indicated that inhibin-alpha 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.