基质Gla蛋白在骨髓间充质干细胞成骨分化中的作用研究

Decreased ability of bone formation is one of the most important mechanisms in the pathogenesis of senile osteoporosis. And it is also closely related with bone marrow mesenchymal stem cells (BMSCs) osteogenic differentiation ability . Matrix Gla protein (MGP) is secreted by bone cells, inhibit mineralization protein. Our previous study founded that (1) MGP involved in bone formation of ovariectomized rats(2)Also the MGP gene expressed in the BMSCs(3)And bone differentiation induced factor Runx2 regulated MGP gene promoter activity.These clues suggest that MGP may induce BMSCs to osteoblastic differentiation.However, its role in bone formation is unclear. To confirm this hypothesis,we will go through (1) compare the ability of osteogenic and it's signaling pathways in MGP gene knock out mice and transgenic mice (2) compare the ability of osteogenic and it's signaling pathways in BMSCs in vitro, after transfecting and silencing of MGP gene . This study will further.reveal new mechanism in the pathogenesis of osteoporosis.

老年性骨质疏松症发病的重要病机制之一是骨形成能力减弱，而骨形成能力又与骨髓间充质干细胞（BMSCs）成骨细胞诱导分化能力密切相关。基质Gla蛋白（Matrix Gla Protein MGP）是成骨细胞分泌，有抑制矿化功能的蛋白。我们前期研究发现（1）MGP参与了去卵巢大鼠骨形成（2）在BMSCs内也有MGP基因表达（3）成骨分化诱导的因子Runx2能调节BMSC内MGP基因启动子的活性。基于前期研究基础，我们推论出MGP可能诱导了BMSCs向成骨细胞分化，有促骨形成的作用这一假说，且其分子机制亦未阐明。我们将通过（1）MGP基因敲除及转基因小鼠BMSCs成骨分化能力、成骨信号通路差异的比较（2）体外观察BMSCs内MGP过表达及MGP基因沉默后成骨能力及信号通路改变来证实这一假说。本研究将进一步从成骨起源深入揭示MGP在骨质疏松发病中的新机制。

老年性骨质疏松症发病的重要病机制之一是骨形成能力减弱，而骨吸收增强成骨及破骨的能力与骨髓间充质干细胞（BMSCs）成骨及破骨细胞细胞诱导分化能力密切相关。基质Gla蛋白（Matrix Gla Protein MGP）是成骨细胞分泌，有抑制矿化功能的蛋白。本项目完成了下列研究（1）MGP转基因小鼠micro-CT 示骨密度及骨微结构得到了明显的改善，体外细胞实验也证实了该结果与诱导BMSCs成骨分化及上调Wnt信号通路有关（2）MGP基因敲除鼠micro-CT 示骨密度下降及骨微结构破坏，体外细胞实验证实MGP调节破骨细胞的分化（3）完成了392例临床患者MGP检测，13例临床患者micro-CT的检测。本研究为骨质疏松的发病机制及临床诊断治疗提供了重要的依据