骨形成蛋白调控成骨分化的信号机制  

Signaling mechanism of osteoblastic differentiation of bone morphogenetic proteins

作　　者：王茸影[1] 易静[1] 

机构地区：[1]上海第二医科大学细胞生物学教研室,上海200025

出　　处：《生命科学》2005年第1期34-39,共6页Chinese Bulletin of Life Sciences

基　　金：国家自然科学基金(30170943)

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。Bone morphogenetic proteins (BMPs) can induce the differentiated function of osteoblastic lineageand nonosteoblastic lineage cells and formation of ectopic bone. BMPs bind to specific receptors and signalsby phosphorylating downstream R-Smads, which form heterodimers with Smad4, and after nuclear transloca-tion regulate transcription factors including Cbfa1, Osterix and Dlx. BMPs can also up-regulate the transcrip-tion factors CIZ and AJ18, I-Smad, soluble protein noggin and germlin, which can antagonize the osteoblasticactivities of BMPs to maintain the skeletal homeostasis. Because of their powerful osteoblastic activities,BMPs have become a clinic research focus on bone regional gene therapy.

关 键 词：骨形成蛋白 核心结合因子-1 OSTERIX Smad DLX CIZ AJl8 

分 类 号：Q513.2[生物学—生物化学] Q254