The Effect Of Follicle-Stimulating Hormone Β-Subunit On Bone Morphogenetic Protein 9-Induced Osteogenic Differentiation In Mouse Embryonic Fibroblasts

PMOP is usually an asymptomatic bone-related disease characterized by reduced bone mineral density(BMD)in aging women,so it is remains a global public health concern,and new effective safe treatments are urgently needed recently.Efficient osteogenesis from MSCs would have the clinical application potential in treating multiple osteal disorders.FSH is a pituitary glycoprotein hormone highly associated with menopausal bone turnover,whose peculiar part of receptor binding is FSHβ.BMP9,a potent osteogenic factor,can up-regulate FSHβ in 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 ALP,the expression of osteogenic transcriptional factors,Runx2 and Osx,and the established late osteogenic markers,OPN and 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,Smad6,and Smad7,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/FSHR/c AMP dependent pathway in MEFs partly.