抗衰老因子GDF11维持骨髓间充质干细胞功能及逆转老年性骨丢失的机制研究

GDF11为新发现的可逆转衰老相关性疾病的循环因子，但其对骨代谢的影响未明。我们首次发现GDF11可以增强骨髓间充质干细胞（BMSCs）的自我更新及克隆形成能力而维持BMSCs的功能，本研究拟从BMSCs功能角度探讨GDF11对骨代谢的作用。首先用青年-老年联体小鼠模型、重组GDF11蛋白干预，升高老年小鼠循环中GDF11水平，观察GDF11对老年小鼠BMSCs的数目，自我更新、克隆形成能力、成骨分化潜能等功能和骨代谢情况的影响；进而构建BMSCs特异性GDF11受体（Activin receptor II）基因敲除小鼠模型，研究GDF11作用阻断对BMSCs及骨量的作用；同时研究阻断Notch信号途径对GDF11作用的影响，解析GDF11对BMSCs影响的信号通路。探讨是否存在抗衰老因子GDF11通过维持BMSCs功能，逆转老年性骨丢失的新机制，为老年性骨质疏松的防治拓展新途径。

GDF11 is the newly discovered circulating factor that can reverse the aging related diseases, but its effect on bone metabolism is unknown. Our pilot work found that GDF11 could maintain the function of bone marrow mesenchymal stem cells (BMSCs) by enhancement of self-renewal and cloning formation ability. This study aims to investigate the effect of GDF11 on bone metabolism through studying BMSCs function. First we will elevate the levels of GDF11 in aging mice circulation by using heterochronic parabiosis model and intervention with recombinant mouse GDF11 protein, and investigate the effect of GDF11 on aging mice BMSCs ,including amount of BMSCs ,self-renewal, colony formation ability, osteogenenic differentiation potential and the process of aging and apoptosis. And then we will construct the BMSCs specific GDF11 receptor (Activin receptor II) gene knockout mice to study the effect of blocking GDF11 on BMSCs and bone mass; The changes of GDF11 on regulating BMSCs was also studied by blocking Notch signal pathway. We hope that illustrating the new mechanism of reversing age-related bone loss by maintaining BMSCs function with anti-aging factor GDF11 will be useful to explore a new way of prevention and treatment for senile osteoporosis.