骨質(zhì)疏松機(jī)制與治療藥靶課件

骨質(zhì)疏松的機(jī)制和治療藥靶骨質(zhì)疏松的機(jī)制1破骨細(xì)胞與骨頭吸收破骨細(xì)胞來源于造血干細(xì)胞,與單核細(xì)胞和巨噬細(xì)胞相系密切。DifewenfipfierM-CSERANK[IL-1]RANKL是破骨細(xì)胞生成的關(guān)鍵因子破骨細(xì)胞與骨頭吸收2破骨細(xì)胞的生成從破骨細(xì)胞monuclear前體分化成多核的破骨(m(leorlasl細(xì)胞主要依賴于RANKLuttar結(jié)合到破骨細(xì)胞中的受體RANK上激活破骨細(xì)m1slonomycin,Thapsigargin,Cyclopiazonic胞RANKL(receptoractivatorofNF-κkBligand):TNF家族成員,起巨噬細(xì)胞集落刺激因子作用,RANKL在成骨細(xì)胞、骨髓基質(zhì)細(xì)胞,以及T和B淋巴細(xì)胞中表達(dá)RANK:RANKL'受體oPG:RANKL的可溶性受體,起抑制信號(hào)作用破骨細(xì)胞的生成3RANK信號(hào)通路RANK有三個(gè)TRAF結(jié)合基序,可募集6種TRAF蛋白基序1募集TRAF6,激活6條主要的信cSB圈RANKCytoplasmicDomain號(hào)通路(Akt,NFATC1,NF-kB,JNK,TAK1TAB1ERKandp38),涉及破骨細(xì)胞的分化、功能和存活,其功能類似于TNF和-1,與免疫應(yīng)答有關(guān)基序2和3與那個(gè)TRAF結(jié)合還不是很清楚,都能激活NFKB,基序2還astlineage激活P38,這兩個(gè)基序涉及破骨細(xì)胞生成,是治療骨質(zhì)疏松的靶點(diǎn)RANK還含有一個(gè)Y基序,結(jié)合與TRAF無關(guān)的信號(hào)蛋白(?)介導(dǎo)Rac的激活,涉及破骨細(xì)胞骨架構(gòu)架和破骨細(xì)胞譜系的定型是治療骨質(zhì)疏松的靶點(diǎn)OsteoclastDifferentiation,Functionand/orSurvivalFATc1,在破骨細(xì)胞前體中表達(dá),是破骨細(xì)胞生成的AF:腫瘤環(huán)死困了受體相關(guān)因子重要調(diào)節(jié)者c1:T細(xì)胞激活核因RANK信號(hào)通路4NFATC1破骨細(xì)胞分化的主要轉(zhuǎn)錄因子成骨細(xì)胞分泌的RANKL和巨噬細(xì)胞集落刺激因子(MCSF),在巨噬細(xì)胞前體中,激活Fos的表達(dá),后者又介導(dǎo)破骨細(xì)胞分化的主要調(diào)節(jié)者-T細(xì)胞激活核因子C1(NFATC1)的表達(dá)破骨細(xì)胞分化NFATC1可誘導(dǎo)破骨細(xì)胞表達(dá)的基因有:抗酒石酸酸性磷酸釃(TRAP)組織蛋白酶K(cathepsinK)氯離通道7(clcn7)MMP-9ephrinB2NFATC1破骨細(xì)胞分化的5骨質(zhì)疏松機(jī)制與治療藥靶課件6骨質(zhì)疏松機(jī)制與治療藥靶課件7骨質(zhì)疏松機(jī)制與治療藥靶課件8骨質(zhì)疏松機(jī)制與治療藥靶課件9骨質(zhì)疏松機(jī)制與治療藥靶課件10骨質(zhì)疏松機(jī)制與治療藥靶課件11骨質(zhì)疏松機(jī)制與治療藥靶課件12骨質(zhì)疏松機(jī)制與治療藥靶課件13骨質(zhì)疏松機(jī)制與治療藥靶課件14骨質(zhì)疏松機(jī)制與治療藥靶課件15骨質(zhì)疏松機(jī)制與治療藥靶課件16骨質(zhì)疏松機(jī)制與治療藥靶課件17骨質(zhì)疏松機(jī)制與治療藥靶課件18骨質(zhì)疏松機(jī)制與治療藥靶課件19骨質(zhì)疏松機(jī)制與治療藥靶課件20骨質(zhì)疏松機(jī)制與治療藥靶課件21骨質(zhì)疏松機(jī)制與治療藥靶課件22骨質(zhì)疏松機(jī)制與治療藥靶課件23骨質(zhì)疏松機(jī)制與治療藥靶課件24骨質(zhì)疏松機(jī)制與治療藥靶課件25骨質(zhì)疏松機(jī)制與治療藥靶課件26骨質(zhì)疏松機(jī)制與治療藥靶課件27骨質(zhì)疏松機(jī)制與治療藥靶課件28骨質(zhì)疏松機(jī)制與治療藥靶課件29骨質(zhì)疏松機(jī)制與治療藥靶課件30骨質(zhì)疏松機(jī)制與治療藥靶課件31骨質(zhì)疏松機(jī)制與治療藥靶課件32骨質(zhì)疏松機(jī)制與治療藥靶課件33骨質(zhì)疏松機(jī)制與治療藥靶課件34骨質(zhì)疏松機(jī)制與治療藥靶課件35骨質(zhì)疏松機(jī)制與治療藥靶課件36骨質(zhì)疏松機(jī)制與治療藥靶課件37骨質(zhì)疏松機(jī)制與治療藥靶課件38