雌二醇对人成骨细胞护骨素、护骨素配体及其相关因子的调节  

The effects of 17β-estradiol on the expression of OPG OPGL and related cytokines in human osteoblasts

作　　者：苏欣[1] 廖二元[1] 朱旭萍[1] 彭健[1] 

机构地区：[1]中南大学湘雅二医院代谢内分泌所,长沙市410011

出　　处：《中华老年医学杂志》2004年第3期153-156,共4页Chinese Journal of Geriatrics

基　　金：国家自然科学基金项目 ( 3 9970 3 47)

摘　　要：目的　观察 17β 雌二醇 (17β E2 )和雌激素受体拮抗剂ICI182 780 (ICI)对人成骨细胞(HOB)表达护骨素 (OPG)、护骨素配体 (OPGL)及其相关因子〔肿瘤坏死因子相关凋亡诱导配体、巨噬细胞集落刺激因子 (TRAIL、M CSF)〕的影响 ,探讨它们在骨转换过程中的重要作用。　方法　接种人成骨细胞 ,再分别用不同浓度 17β E2 和ICI干预 ,用RT PCR法检测基因表达情况 ,用Westernblot分析法检测蛋白表达情况。　结果　 (1) 17β E2 能上调人成骨细胞中OPG的表达 ,下调OPGL、M CSF及TRAIL的表达 ;(2 )ICI对被检基因有不同的调节活性 ,与 17β E2 合用时 ,表现出对后者的拮抗作用或协同作用。　结论　雌激素缺乏时 ,成骨细胞中OPG的表达减少 ,而OPGL、M CSF和TRAIL等细胞因子的表达增加 ,使破骨细胞的数量和活性增加 ,导致骨吸收增强和骨量丢失 ,这可能是绝经后骨质疏松症的重要的发病机制之一 ;ICI在对雌激素受体调节中 ,具有拮抗和激动的双重效应 。Objective To observe the regulative effects of 17β-estradiol(E 2) and ICI182780 on the expression of osteoprotegerin(OPG),the ligand of osteoprotegerin (OPGL) and the related cytokines (M-CSF and TRAIL) in human osteoblasts(HOBs) and to investigate their important roles in the process of bone turnover. Methods The expression of OPG,OPGL,M-CSF and TRAIL mRNA were examined by RT-PCR. The expression of OPG and OPGL protein were measured by Western blot. Results 17β-E 2 up-regulated the expression of OPG but down-regulated OPGL,M-CSF andTRAIL expression in HOBs. ICI182780 showed varied transactivating capability while regulating the expression of OPG, OPGL, TRAIL and M-CSF genes in HOBs. It showed estrogen antagonism or partial estrogen agonism when used together with 17β-E 2 under different conditions. Conclusions (1)Postmenopausal osteoporosis due to estrogen deficiency leads to the decreased expression of OPG but the increased expression of some bone-resorbing cytokines as OPGL, M-CSF and TRAIL in osteoblasts,then stimulates osteoclast differentiation and activity,which potentiates the bone resorption and bone loss;(2)ICI182780 shows partial transactivating activity in osteoblasts, so it might be a kind of selective estrogen receptor modulators(SERM).

关 键 词：雌二醇 成骨细胞 护骨素 护骨素配体 细胞因子 骨质疏松症 

分 类 号：R96[医药卫生—药理学]