BMP9调控MSCs成骨分化的分子机制一直尚未阐明。前期结果提示BMP9极可能经PI3K/AKT途径调控MSCs成骨分化。本项目利用放射自显影、ELISA和Western进一步证实BMP9/PI3K/AKT途径在MSCs中的存在；Co-IP，GST pull down等证实BMP9可通过其受体活化PI3K/AKT途径；细胞实验和动物实验分析BMP9/PI3K/AKT途径对MSCs成骨分化的调控作用；最后解析BMP9/PI3K/AKT途径调控MSCs成骨分化的分子机制，重点关注其影响Smad途径、影响细胞周期和增殖、影响成骨关键转录因子、影响mTOR、经GSK3β与Wnt/β-catenin途径交互对话而调控成骨分化，并利用抗体芯片及基因芯片寻找更多与BMP9/PI3K/AKT途径调控MSCs成骨分化相关的信号分子或下游靶基因。研究结果将进一步丰富BMP9调控MSCs成骨分化的信号网络。

Although previous studies have demonstrated that BMP9 is a more potent inducer in promoting osteogenic differentiation of mesenchymal stem cells (MSCs), the precise molecular mechanism involved remains to be fully elucidated. The latest experimental results implied us that BMP9 is possible to regulate osteogenic differentiation of MSCs via activation of PI3K/AKT pathway. However,the molecular mechanism through which BMP9/PI3K/AKT pathway regulates osteogenic differentiation of MSCs is still largely unknown and warrants extensive studies. For this purpose, we used autoradiography, ELISA and Western blot to further validate the existence of BMP9/PI3K/AKT pathway in MSCs. Moreover, co-immunoprecipitation, GST pull down was carried out to confirm that BMP9 could activate PI3K/AKT pathway through its receptors. Subsequently, using in vitro cell experiments and in vivo animal experiment, the exact role of BMP9/PI3K/AKT pathway on regulating osteogenic differentiation of MSCs was intensively analyzed. Finally, the detail molecular mechanism underlying BMP9/PI3K/AKT pathway-regulated osteogenic differentiation of MSCs was illuminated, mainly focusing on the influence on classical Smad pathway, the influence on cell cycle and proliferation, the influence on osteogenic transcription factors, the influence on mTOR, and on crosstalking with Wnt/β-catenin pathway through GSK3β. Nevertheless, AKT phosphorylation antibody array and PI3K/AKT signal pathway microarray were used to identify new moleculars and downstream target genes involved in BMP9/PI3K/AKT pathway-regulated osteogencic differentiation of MSCs. This project will provide new insights into signal network by which BMP9 induces osteogenic differentiation of MSCs，and will provide more experimental dada for clinical application of BMP9.