Study Of The Facilitating Functions Of FSH? On BMP9-induced Osteogenic Differentiation Of MSCs And The Mechanism

PMOP has become a global public health problem,increasing disability and mortality in elderly women.The relationship PMOP between FSH has also received extensive attentions.MSCs as one of the most important cells in tissue engineering,more and more attention have been paid to understand the mechanism of osteogenic differentiation in its multidirectional differentiation potential.BMPs family has been used in the treatment of bone formation and fractures,but BMP9 is one of the strongest factors in inducing heterotopic osteogenesis,has no clinical application at present,so we want to understand the mechanism of its function.Therefore,in this study,we explored the role of FSH? on BMP9-induced osteogenic differentiation of mesenchymal stem cells,and try to find the possible mechanism underlying this process.We found that FSH? significantly increased the expression levels of BMP9-induced early osteogenic marker ALP and late osteogenic markers OCN,COL 1a1,OPN,calcium salt nodule and osteogenic transcription factor Osx,and the same changes were observed in heterotopic bone formation.In terms of mechanism,FSH?significantly increased the transduction of Notch classical signaling pathway in BMP9-induced differentiation of mesenchymal stem cells,including the expression levels of receptors Notch3/4,and target genes Hes1 and Hey1 mRNA.Moreover,the use of DAPT,as ?-secretaseinhibitor,reduced the expression levels of Notch signal target genes.In addition,DAPT also reduced the expression levels of early and late markers enhanced by FSH? in BMP9-induced osteogenic differentiation.In conclusion,our results indicated that FSH? could increase BMP9-inducted osteogenic differentiation in mesenchymal stem cells,and Notch may be an important mediating signal in this process.Therefore,this study may provide a new direction for the prevention and treatment of postmenopausal osteoporosis and the study of tissue engineering bone.