《生命科学》 2005, 17(1): 34-39

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：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

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: Abstract:  Bone morphogenetic proteins (BMPs) can induce the differentiated function of osteoblastic lineage and nonosteoblastic lineage cells and formation of ectopic bone.  BMPs bind to specific receptors and signals by phosphorylating downstream R-Smads， which form heterodimers with Smad4， and after nuclear translocation regulate transcription factors including Cbfa1， Osterix and Dlx. BMPs can also up-regulate the transcription factors CIZ and AJ18， I-Smad， soluble protein noggin and germlin， which can antagonize the osteoblastic activities 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.
Key words:  BMP; Cbfa1; Osterix; Smad; Dlx; CIZ; AJ18