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

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.

Huang M ，Cheng YL ，Zeng JT ，Su XY ，Liu H ... -  《-》

Hey1 basic helix-loop-helix protein plays an important role in mediating BMP9-induced osteogenic differentiation of mesenchymal progenitor cells.

Sharff KA ，Song WX ，Luo X ，Tang N ，Luo J ，Chen J ，Bi Y ，He BC ，Huang J ，Li X ，Jiang W ，Zhu GH ，Su Y ，He Y ，Shen J ，Wang Y ，Chen L ，Zuo GW ，Liu B ，Pan X ，Reid RR ，Luu HH ，Haydon RC ，He TC ... -  《-》

Schnurri-3 regulates BMP9-induced osteogenic differentiation and angiogenesis of human amniotic mesenchymal stem cells through Runx2 and VEGF.

Li Y ，Liu Z ，Tang Y ，Feng W ，Zhao C ，Liao J ，Zhang C ，Chen H ，Ren Y ，Dong S ，Liu Y ，Hu N ，Huang W ... -  《Cell Death & Disease》

Identification and analysis of type II TGF-β receptors in BMP-9-induced osteogenic differentiation of C3H10T1/2 mesenchymal stem cells.

Wu N ，Zhao Y ，Yin Y ，Zhang Y ，Luo J ... -  《-》

Follicle-Stimulating Hormone β-Subunit Potentiates Bone Morphogenetic Protein 9-Induced Osteogenic Differentiation in Mouse Embryonic Fibroblasts.

Postmenopausal osteoporosis (PMOP)-related fractures usually result in morbidity and mortality in aging women, so it remains a global public health concern, and new effective safe treatments are urgently needed recently. Efficient osteogenesis from mesenchymal stem cells (MSCs) would have the clinical application potential in treating multiple osteal disorders. Follicle-stimulating hormone (FSH), a pituitary glycoprotein hormone highly associated with menopausal bone turnover, whose peculiar part of receptor binding is follicle-stimulating hormone β-subunit (FSHβ). Bone morphogenetic protein 9 (BMP9), a potent osteogenic factor, can up-regulate FSHβ in mouse embryonic fibroblasts (MEFs). However, it is unclear, whether extrapituitary FSHβ affects BMP9-induced osteogenesis in MEFs. In this study, we investigated the role of FSHβ in BMP9-induced osteogenesis in MEFs. We found that exogenous expression of FSHβ significantly increased BMP9-induced alkaline phosphatase activity (ALP), the expression of osteogenic transcriptional factors, Runx2 and Osx, and the established late osteogenic markers, osteopontin (OPN) and osteocalcin (OCN), so does the ectopic bone formation. Mechanistically, FSHβ dramatically enhanced BMP9-induced BMP/Smad signal transduction, presenting the augment phosphorylation of Smad1/5/8, whereas treatment with anti-FSHβ antibodies suppressed these effects. An adenylate cyclase inhibitor obviously suppressed ALP and BMP/Smad signal transduction induced by BMP9 or the combination of BMP9 and FSHβ in MEFs. Collectively, our findings suggested that FSHβ may promote BMP9-induced activation of BMP/Smad signaling through a FSH/FSH receptor (FSHR)/cAMP dependent pathway in MEFs partly. J. Cell. Biochem. 118: 1792-1802, 2017. © 2016 Wiley Periodicals, Inc.

Su XY ，Zou X ，Chen QZ ，Zeng YH ，Shao Y ，He BC ，Liu H ... -  《-》