骨髓间充质干细胞向成骨细胞分化及成骨细胞向骨细胞的终末分化参与骨发育与重塑、骨质疏松和骨肿瘤等多种生理病理过程，但其调控机制尚不明了。前期实验中我们发现敲除小鼠骨形态发生蛋白IA型受体（BMPRIA）后，在长骨中出现大量松质骨，组织学检测显示成骨细胞数量明显增加，而成骨细胞的增殖活性、凋亡率及破骨细胞数量没有明显变化，即敲除BMPRIA主要通过增加增加间充质细胞向成骨细胞分化而促进成骨；但在骨量增加的同时，骨强度和骨中胶原蛋白含量下降。这些结果提示BMPRIA在调控成骨细胞数量及其终末分化中起到关键作用。本项目将在此基础上，通过基因敲除和挽救、实时定量PCR等方法，探讨BMPRIA在调控成骨细胞数量及其终末分化中的下游信号通路及其作用机制。相关研究将初步阐明BMPRIA调控骨髓间充质干细胞和成骨细胞分化的机制，有助于了解骨质疏松和骨肿瘤等发生机制，并丰富干细胞分化的基础理论。

Differentiation of bone marrow-derived mesenchymal stem cells to osteoblasts and the terminal differentiation of osteoblasts to osteocytes participate in many physiopathological processes such as bone development, bone remodeling, osteoporosis and bone-related tumor, however, the mechanisms regulating these processes are now unclear. Our previous studies showed that deletion of type IA receptor for bone morphogenic protein (BMPR1A) in mice led to massive bone formation in long bone, significant increase of the number of ostoeblasts and no significant changes of the proliferation ability of osteoblasts, apoptosis of osteoblasts and the number of osteoclasts. BMPR1A knockout also resulted in lowered bone intensity and decreased bone collage. These results indicated that BMPR1A played an important role in regulating the differentiation of bone marrow-derived mesenchymal stem cells to osteoblasts and the terminal differentiation of osteoblasts to osteocytes. Based on these findings, the involved signaling pathway and the possible mechanisms of BMPR1A in regulating the number and terminal differentiation of osteoblasts will be investigated in this project by means of gene deletion, gene rescue and Real-time PCR, et al. Related research will tell preliminarily the mechanisms of BMPR1A in regulating the differentiation of mesenchymal stem cells and osteoblasts, shed light on the mechanism of the development of ostroporosis and bone-related tumor, and enrich the basic theory of stem cell differentiation.