骨形态发生蛋白2通过Smad途径上调Osterix的表达  

Bone Morphogenetic Protein 2 Upregulates Osterix Expression Through Smad Pathway

作　　者：潘秋辉[1] 李益广[2] 杨松海[2] 马纪[2] 谢在春[3] 于永春[3] 孙奋勇[2] 

机构地区：[1]中山大学附属第二医院医学研究中心,广州510120 [2]暨南大学生命科学技术学院生物工程研究所,广州510632 [3]同济大学附属第十人民医院科教科,上海200071

出　　处：《中国生物化学与分子生物学报》2008年第1期40-45,共6页Chinese Journal of Biochemistry and Molecular Biology

基　　金：国家自然科学基金项目(No30600328);广州市科技计划项目(No2006Z1-E0031)资助课题~~

摘　　要：Osterix(Osx)是一种重要的调控成骨细胞分化的具有锌指结构的转录因子.骨形态发生蛋白2(bone morphogenetic protein 2,BMP 2)能够上调Osx的表达,但其分子机制并不清楚.采用实时定量RT-PCR方法检测到BMP2诱导成骨相关细胞C3H10T1/2,MC3T3-E1,C2C12中Osx的转录水平显著上调,并且与成骨分化指标Col1a1,osteocalcin具有相似的表达动力学特征.而且,在C3H10T1/2细胞中过表达负显性(dominant negative,DN)Osx基因,能够有效抑制BMP2诱导的成骨分化.过表达BMP/Smad信号通路抑制蛋白Smad6,能够抑制Osx转录水平的上调.但是通过荧光素酶报告载体对Osx的启动子-1254^+85区域进行分析后未发现接受BMP通路调控的启动子区域.上述结果表明,BMP2能够通过Smad途径上调Osx的表达,并对成骨分化的过程具有十分重要的作用.Osterix （Osx） is a zinc-finger-containing transcription factor which plays an important role in osteogenesis. Bone morphogenetic protein 2 （BMP2） may increase the transcription of Osx in osteoblast, but the mechanism remains unclear. The Osx transcription level in MC3T3-E1, C2C12 and C3H10T1/2 cell line, which possess osteoblast phenotypes, were analyzed by realtime quantitative RT-PCR. Following BMP2 stimulation, the Osx levels were significantly upregulated, with the same induction kinetics as the important osteogenesis markers Collal and osteocalcin. In addition, the introduction of a dominant negative Osx remarkably blocked the differentiation of C3H10T1/2 into osteocytes. The overexpression of Smad6, an inhibitor of BMP/Smad pathway, effectively diminished the BMP-induced upregulation of Osx in C3H10T1/2. The - 1 254～ ＋ 85 bp of Osx promoter was cloned into a luciferase reporter plasmid, but response of BMP2 regulation to this region was not observed. Our results suggest that BMP2 upregulates Osx expression through the Smad pathway which is important for osteocyte differentiation.

关 键 词：OSTERIX 成骨细胞 骨形态发生蛋白2 

分 类 号：Q78[生物学—分子生物学]