| Backgroud:Estrogen as a steroid hormoneis essential for the growth and development of women,which play a pivotal role in promoting the development of women's reproductive organs,maintain the second sexual characteristics,as well as regulating the osteoblasts and osteoclasts.Osteoporosis is divided into primary and secondary,and primary osteoporosis is common in the elderly population,especially in postmenopausal women due to lacking of estrogen.The International Menopausal Society in 2013 indicated that perimenopausal and postmenopause women with application of menopausal hormone therapy(MHT)early can relieve bone loss,but the specific mechanism is not clear.Currently,theres researches showed that the postmenopausal osteoporosis was regulated by Wnt16/?-catenin pathway and OPG/RANK/RANKL system.Wnt16 belongs to the family of Wnt,which is composed of highly conserved secretory glycoproteins and participated in the regulation of osteoblasts and osteoclast activity.In the canonical WNT pathway,engagement of Wntl6 with their receptors,results in the activation of Wnt16/?-catenin pathway,transcriptional activation of osteoblast-related genes and maintains bone density.The receptor activator of nuclear factor-kB ligand(RANKL)is a membrane-binding protein that was expressed in osteoblasts and stromal cells and can be decomposed into soluble RANKL(sRANKL)by metalloproteinases.RANKL with their receptorspromoted osteoclasts somatic cell differentiation and maturation,and enhanced osteoclast bone resorption.OPG belongs to the tumor necrosis factor(TNF)receptor superfamily is a secretory glycoprotein.Osteoblasts and bone marrow stromal cells express OPG,which competitively combines with RANKL to inhibit osteoclast generation,maturation and induce osteoclast apoptosis.However,whether estrogen regulateing the Wnt16/?-catenin pathway,OPG/RANK/RANKL system plays a role in bone protection is not clear.Therefore,this study tests the success of peri-menopausal osteoporosis model by analysising the microscopic morphology of bone tissue.Second,from the Wnt16/(3-catenin pathway,OPG/RANK/RANKL system,we study the mechanism of estrogen slow down bone loss in early menopause.Finally,through compared different time of mutual comparison,we revealed the role of estrogen in this time-dependent.Objective:To investigate the expression of Wnt16,?-catenin,OPG and RANKLin bone loss in a pastmenopausal osteoporosis(PMO)rat mode with ovarletomy(OVX),and to explore the protective effects of exogenous estrogen in bone tissue.Methods:The40 female Wistar rats were randomly divided into sham operation group,ovariectomized group,experimental group 1 and experimental group 2.In the experimental group,17?-E2 was injected subcutaneously for 4 weeks and 16 weeks,respectively.The other two groups were given the same volume of normal saline.Theserum E2 level was determined by ELISA,the expression of Wnt16,OPG,RANKL and?-catenin in bone tissue were measured after 16 weeks.The thickness of the trabecular bone(Tb.Th),number of trabecular bone(Tb.N)and thetrabecular spacing(Tb.SP)were measuredusing HE staining analysis.Results:The sham operationgroup and experimental group 2 compared with the ovariectomized group,the levels of OPG,?-catenin,Wnt16 mRNA,serum E2,Tb.Th and Tb.Nwere significantly increased,the level of RANKL and Tb.SP were significantly decreased(all P<0.05).The experimental group 1 compared with the ovariectomized group,the levels of?-catenin,serum E2,Tb.Thand Tb.Nwere significantly increased,the level of RANKL and Tb.SP were significantly decreased(all P<0.05).Conclusion:Estrogen may prevent osteoporosisby upregulating Wnt16,?-catenin,OPG and downregulating RANKL. |
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