17-β雌二醇对去卵巢大鼠成骨细胞间质胶原酶MMP-8,MMP-13及其抑制因子TIMP-1表达的作用  

Effect of 17-β estradiol on expression of interstitial ccollagenases and tissue inhibitor of metalloproteinase in osteoblasts of ovariectomized rat model

作　　者：蒋谊[1] 廖二元[1] 戴如春[1] 魏启幼[1] 罗湘杭[1] 

机构地区：[1]中南大学湘雅二医院,长沙410011

出　　处：《中国骨质疏松杂志》2004年第2期129-134,共6页Chinese Journal of Osteoporosis

基　　金：国家自然科学基金资助项目(39970347)

摘　　要：目的 研究17-β雌二醇(E2)对成骨细胞间质胶原酶MMP-8、MMP-13和组织基质金属蛋白酶抑制剂TIMP-1的调控作用,探讨绝经后骨质疏松的发病机制。方法 利用去卵巢大鼠骨质疏松(OVX)模型,观察E2治疗对骨组织形态计量学参数的影响;采用免疫组化和原位杂交的方法,检测其胫骨近端成骨细胞中MMP-8、:MMP-13、TIMP-1 mRNA和蛋白表达水平的改变。结果OVX组大鼠与E2治疗组相比,骨量丢失明显,成骨细胞中MMP-13 mRNA和蛋白的表达水平显著升高,而MMP-8、TIMP-1 mRNA与蛋白的表达无明显改变。相关分析表明MMP-13蛋白表达水平与骨小梁间隔(Tb.Sp)、骨小梁类骨质表面积(OS/TBA)呈正相关,与骨小梁数目(Tb.N)、骨小梁占全部骨组织体积比(TBV/TTV)呈负相关。结论 MMP-13在雌激素缺乏性骨量丢失中起重要作用。雌激素可通过下调成骨细胞中MMP-13的表达,抑制骨吸收,降低骨转化率,防治绝经后骨质疏松症的发生。Objective To characterize the effects of 17-β estradiol (E2) on the expression of interstitial collagenases MMP-13, MMP-8 and tissue inhibitor of metalloproteinase TIMP-1 in osteoblast of bone tissue in order to elucidate the molecular mechanism of postmenopausal osteoporosis. Methods The adult ovariectomized rat (OVX) models with osteoporosis were used in this study to investigate the changes of bone histomorphometric pa-rameters after treatment with E2. The expressions of MMP-13, MMP-8, TIMP-1 mRNA and protein were analysed, respectively by immunohistochemistry and in situ hybridization.Results Compared with E2-treated rats, the ex-pression of MMP-13 mRNA and protein but not MMP-8 or TIMP-1 in OVX rats increased significantly, accompa-nied by large quantity of bone loss in trabecular bones. Furthermore, the expression of MMP-13 protein showed positive correlation with Tb. Sp and TBV/TTV,and negative correlation with Tb.N and OS/TBA. Conclusion Overexpression of MMP-13 plays an important role in the estrogen-deficient bone loss. Estrogen inhibits bone re-sorption and decreases the bone turnover rates by down-regulating the MMP-13 expression in osteoblast to prevent and treat osteoporosis.

关 键 词：17-Β雌二醇 去卵巢 大鼠 成骨细胞 间质胶原酶 MMP-8 MMP-13 TIMP-1 组织基质金属蛋白酶抑制剂 绝经后 骨质疏松 发病机制 

分 类 号：R681[医药卫生—骨科学] R977.12[医药卫生—外科学]