骨形成蛋白调控成骨分化的信号机制.PDFVIP

第17卷 第1期 生命科学 Vol. 17, No. 2005年2月 Chinese Bulletin of Life Sciences Feb., 2005 文章编号：1004-0374(2005)01-0034-06 骨形成蛋白调控成骨分化的信号机制 王茸影，易 静* （上海第二医科大学细胞生物学教研室，上海200025） 摘　要：骨形成蛋白(bone morphogenetic proteins, BMPs)能诱导成骨细胞和软骨细胞的分化成熟，并 能在体内诱导异位成骨。BMPs与骨形成蛋白受体BMPR结合，通过Smads和p38 MAPKs途径进行 信号转导，并通过下游转录因子Cbfa1、Osterix、Dlx等与相应的成骨细胞特异蛋白碱性磷酸酶、骨 钙素、OPN等基因启动子连接，促进细胞向成骨方向分化。另外，还通过转录因子CIZ、AJ18等 对成骨进行负调控，维持胚胎发育正常，保持骨量平衡。由于BMPs在骨修复中的重要作用，现已 成为基因治疗用于骨缺损的一个研究热点。 关键词：骨形成蛋白;核心结合因子-1; Osterix; Smad; Dlx; CIZ; AJ18 中图分类号：Q513.2; Q254　　文献标识码：A Signaling mechanism of osteoblastic differentiation of bone morphogenetic proteins WANG Rong-Ying, YI Jing* (Department of Cell Biology, Shanghai Second Medical University, Shanghai 200025, China) Abstract: Bone morphogenet ic proteins (BMPs) can induce the differentiated function of ost eoblast ic lineage and nonosteoblastic lineage cells and formation of ectopic bone. BMPs bind to specific receptors and signals by phosphorylat ing downstream R- Smads, which form heterodimers with Smad4, and after nuclear transloca- tion regulat e tr anscr iption factors including Cb fa 1, Osterix and Dlx. BMPs can also up-regulat e the transcr ip- tion factors CIZ and AJ 18, I- Smad, soluble protein noggin and germlin , which can antagonize the osteoblastic activities of BMPs to m aintain the skelet al hom eost asi s. Becau se of their p ower ful ost eoblastic act ivit ies, BMPs have become a clinic resear ch focu s on bone regional gene therapy. Key words: BMP; Cbfa1; Osterix; Smad; Dlx; CIZ; AJ18 [1] Hanamura和Urist将植入肌肉的脱钙骨基质中 成、肾的发生、肝脏的发育等