Premium
Follicle‐Stimulating Hormone β‐Subunit Potentiates Bone Morphogenetic Protein 9‐Induced Osteogenic Differentiation in Mouse Embryonic Fibroblasts
Author(s) -
Su XiaoYa,
Zou Xiang,
Chen QianZhao,
Zeng YuHua,
Shao Ying,
He BaiCheng,
Liu Hong
Publication year - 2017
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.25849
Subject(s) - smad , medicine , endocrinology , follicle stimulating hormone receptor , bone morphogenetic protein , signal transduction , osteopontin , chemistry , follicle stimulating hormone , runx2 , osteocalcin , microbiology and biotechnology , alkaline phosphatase , transforming growth factor , biology , hormone , luteinizing hormone , biochemistry , enzyme , gene
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.