关键词: BMP9 inhibin-α mesenchymal stem cells osteogenic differentiation

Mesh : Animals Bone and Bones / cytology metabolism Cell Differentiation Cell Line Core Binding Factor Alpha 1 Subunit / genetics metabolism Female Gene Expression Regulation Growth Differentiation Factor 2 Growth Differentiation Factors / genetics metabolism HEK293 Cells Humans Inhibins / genetics metabolism Mesenchymal Stem Cells / cytology metabolism Mice Mice, Nude NF-kappa B / genetics metabolism Osteoblasts / cytology metabolism Osteogenesis / genetics Osteoprotegerin / genetics metabolism RANK Ligand / genetics metabolism Rats Signal Transduction Smad6 Protein / genetics metabolism Smad7 Protein / genetics metabolism Transfection

来  源:   DOI:10.1002/jcb.26843

Abstract:
Inhibin-α, a member of the transforming growth factor (TGF-β) 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-α 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-α on BMP9-induced osteogenic differentiation in MSCs and tried to discover the mechanism underlying this process. We found inhibin-α 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-α. For mechanism, we found that exogenous expression of inhibin-α inhibits BMP9-induced osteogenic differentiation through blocking BMP/Smad signal transduction and activating NF-κB signal which is repressed by BMP9. Thus, our findings indicated that inhibin-α 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.
摘要:
暂无翻译
公众号