title: Follicle-Stimulating Hormone β-Subunit Potentiates Bone Morphogenetic Protein 9-Induced Osteogenic Differentiation in Mouse Embryonic Fibroblasts.
abstract: 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.
authors.affiliation: Department of Reproduction Health and Infertility, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
authors.forename: Xiao-Ya
authors.initials: XY
authors.lastname: Su
authors.affiliation: Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing, 400016, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Zou
authors.affiliation: Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing, 400016, China.
authors.forename: Qian-Zhao
authors.initials: QZ
authors.lastname: Chen
authors.affiliation: Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing, 400016, China.
authors.forename: Yu-Hua
authors.initials: YH
authors.lastname: Zeng
authors.affiliation: Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing, 400016, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Shao
authors.affiliation: Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing, 400016, China.
authors.forename: Bai-Cheng
authors.initials: BC
authors.lastname: He
authors.affiliation: Department of Reproduction Health and Infertility, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
authors.forename: Hong
authors.identifier: 0000-0003-0070-6049
authors.initials: H
authors.lastname: Liu
mesh_terms: D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002460:Cell Line; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D037201:Follicle Stimulating Hormone, beta Subunit / Q000494:pharmacology*; D055427:Growth Differentiation Factor 2; D055412:Growth Differentiation Factors / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D010012:Osteogenesis / Q000187:drug effects / Q000235:genetics; D011962:Receptors, FSH / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D037201:Follicle Stimulating Hormone, beta Subunit; C525887:GDF2 protein, human; D055427:Growth Differentiation Factor 2; D055412:Growth Differentiation Factors; D011962:Receptors, FSH; D000469:Alkaline Phosphatase
keywords: BMP/Smad SIGNALING; BMP9; FSHβ; MEFs; OSTEOGENIC DIFFERENTIATION