基质GLA蛋白在绝经后骨质疏松症骨形成中的作用及分子机制

Matrix gla protein (MGP) is a gamma-carboxylated extracellular matrix protein as an inhibitor of vascular calcification. Both the postmenupausal osteoporosis(PMOP) and vascular calcification are common disease in old women，the common mechanism they shared may be the key point to further insight into mechanism of PMOP. Our preliminary studies have find out that estrogen elevated the expression of MGP in the serum, bone tissue, and osteoblasts in variectomized Sprague-Dawley rats,but the inhibitor of wnt singal path down-regulated the MGP expression.These results indicated that MGP is important in bone formation metabolism in PMOP.It is the rare study on the effect of MGP on the mechanmism of PMOP. we will like to observe the changes on signaling pathway of osteocytes（Wnt, EK1）,expression of bone formation proteins， the proliferation ,differentiation ,apopotisis and mineralization of osteoblasts in osteoblast and in vivro ,in which MGP gene was transfected .Then, we will find out the effects of MGP gene on bone metabolism directly by knocking-in MGP gene to the mice and studying the characteristics on bone biochemical markers, bone immunohistochemistry, and bone ultrastructure. At last, the serum and bone samples,primary osteoblasts of patient who suffered from postmenopausal osteoporosis will be collected. The effect of MGP on bone metabolism will be observed by above-mentioned methods. Our study will begin to make the basic medical research transform to clinic medical research, raise a new theory about the PMOP,laying foundations on finding out the new methods of preventive treatment on PMOP.

基质GLA蛋白（MGP）是一种γ-谷氨酸羧化的细胞外基质蛋白，能抑制血管钙化。绝经后骨质疏松症(PMOP)与血管钙化是老年女性常见且同时存在的疾病,两者共同的发病机制可能是深入了解PMOP发病机制的切入点。我们的前期研究发现，雌二醇发挥骨保护作用的同时也能上调去卵巢（OVX）大鼠血清、骨组织、成骨细胞内MGP表达，Wnt信号通路阻断剂下调这种MGP表达,提示MGP可能在PMOP骨形成过程中起重要的作用。然而目前国内外关于MGP在PMOP骨形成中的机制仍不清楚。申请人拟通过体外成骨细胞转染MGP基因，研究其信号通路(Wnt、EK1)、增殖、分化、凋亡、矿化和骨形成蛋白的变化；通过转MGP基因小鼠OVX模型及临床PMOP患者血清和骨组织MGP表达,研究MGP对骨生化标志物、骨微结构的影响。该研究将提出PMOP发病机制的新理论，初步实现基础研究向临床的转化，为寻找新的PMOP防治方法奠定基础。

基质GLA蛋白（MGP）是一种γ-谷氨酸羧化的细胞外基质蛋白，能抑制血管钙化。绝经后骨质疏松症(PMOP)与血管钙化是老年女性常见且同时存在的疾病,两者共同的发病机制可能是深入了解PMOP发病机制的切入点。我们的前期研究发现，雌二醇发挥骨保护作用的同时也能上调去卵巢（OVX）大鼠血清、骨组织、成骨细胞内MGP表达，Wnt信号通路阻断剂下调这种MGP表达,提示MGP可能在PMOP骨形成过程中起重要的作用。然而目前国内外关于MGP在PMOP骨形成中的机制仍不清楚。申请人通过体外成骨细胞转染MGP基因，研究其信号通路(Wnt)、增殖、分化、凋亡、矿化和骨形成蛋白的变化；通过转MGP基因小鼠OVX模型及临床PMOP患者血清和骨组织MGP表达,研究MGP对骨生化标志物、骨微结构的影响。该研究将提出PMOP发病机制的新理论，初步实现基础研究向临床的转化，为寻找新的PMOP防治方法奠定基础。