The Effect Of Estrogen On Inflammatory Cytokines And Osteogenic Differentiation In LPS Induced RBMSCs

Chronic periodontitis is a destructive and inflammatory disease that manifestsclinically as gingivaltitis, alveolar bone resorption, gingival atrophy and then loose andloss of the teeth. Periodontal pathogens and their metabolites, especiallylipopolysaccharide（LPS）is the main cause of the destruction process. LPS can induceimmune reaction of the host, activate the secretion and expression of inflammatory factors.Estrogens play an essential role in skeletal homeostasis and chronic periodontitis. Rapidpostmenopausal osteoporosis is also concerned with estrogen deficiency. At present themechanism how estrogen influence periodontal tissue is not clear. Bone marrowmesenchymal stem cells (BMSCs) are multipotent stem cells and can differentiate intomany tissue and cells in special culture situation, so BMSCs present them as an ideal stemcell candidate for tissue engineering. In present study, the purpose is to know whetherestrogen can influence the expression of inflammatory factors of BMSCs and regulatebone differentiation of BMSCs, if they are transplantated into periodontal defection, andtry to provide a new method for periodontitis treatment.The research consists the following objectives:1.Isolate and then culture the rat bone marrow mesenchymal stem cells (BMSCs) andidentify them.2.Evaluate what maybe the influence of estrogen to the expression of inflammatory factors in BMSCs induced by LPS.3.Evaluate what maybe the regulation mechanism of estrogen to the expression ofinflammatory factors in BMSCs induced by LPS.4.Evaluate the effects of estrogen on bone differentiation in BMSCs induced by LPS.5.Evaluate the regulation of inflammatory factors to the expression of OPG/RANKLin BMSCs induced by LPS.We harvested the following conclusions:1.The BMSCs can be isolated, purified, cultured and amplified from bone marrow.They can be identified by bionomics and flow cytometry analysis.2.BMSCs induced by LPS can highly expressed TNF-α, IL-1β and IL-6, and E2significantly suppressed this high production dose-dependently. Anti-inflammatory actionof E2was obviously indicated.3.The secretion of inflammatory cytokines of BMSCs was up rising in6h, andpeaked in12h until24h, and then descended in48h and72h as time goes under thecostimulation of LPS and E2.4.The MAPK signaling pathways may be one kind of the channals in the functions ofE2.5.E2can up-regulate OPG production significantly, whereas LPS can up-regulateRANKL production. E2may promote bone differentiation of BMSCs in inflammationenvironment by altering the OPG/RANKL ratio.6.After the action of LPS and E2,the expression of OPG was up rising in6h, andpeaked in12h until24h, and then descended as time goes by. The expression of RANKLwas up rising in6h, and kept high level after12h.7.E2modulates the expression of OPG/RANKL in BMSCs induced by LPS in theway of regulating inflammatory cytokines, which was included in biological function ofE2.