Hedgehog信号途径调控BMP9诱导的间充质干细胞成骨分化

骨缺损修复是临床一大难题。BMP9具有强效诱导间充质干细胞（Mesenchymal Stem Cells，MSCs)成骨分化的能力，这为以MSCs为基础的骨缺损修复带来希望。但目前对BMP9诱导MSCs成骨分化分子机制的理解，仍不够深入。课题组前期发现Hedgehog信号途径可能对BMP9诱导MSCs成骨分化有调控作用。在此基础上，本项目首先确认BMP9是否可活化MSCs中Hedgehog信号；随后分析Hedgehog信号对BMP9诱导MSCs成骨分化的调控作用及特点，并解析Hedgehog信号调控BMP9诱导的MSCs成骨分化分子机制；最后探索利用Hedgehog家族成员Shh来增强BMP9诱导的MSCs成骨分化，从而促进骨折愈合和骨缺损修复的可行性。研究结果将进一步丰富对BMP9调控MSCs成骨分化复杂信号网络的认识和理解，并为BMP9将来在临床用于骨折和骨缺损治疗提供理论和实验依据。

The treatment of bone defect is still a major clinical problem. BMP9 has strong potential to induce osteogenic differentiation of Mesenchymal Stem Cells (MSCs), and brings hope to the MSCs-based bone defect treatment. However, the precise molecular mechanism involved in BMP9-induced osteogenic differentiation of MSCs remains to be fully elucidated. Our recent preliminary results showed that Hedgehog signal pathway is likely to regulate BMP9-induced osteogenic differentiation of MSCs. Based on these results, we will firstly try to validate if BMP9 can activate Hedgehog signal pathway in MSCs. Secondly we will analyze and characterize the effect of Hedgehog signal pathway on BMP9-induced osteogenic differentiation of MSCs. Subsequently, we will investigate the molecular mechanisms through which Hedgehog signal pathway to regulate BMP9-induced osteogenic differentiation of MSCs. Finally, we will explored the feasibility of using Shh, a Hedgehog family member, to enhance BMP9-induced osteogenic differentiation of MSCs, thus to promote fracture healing and to accelerate bone defect repairing. Collectively, this project will further enrich our understanding of the complex signal network involved in BMP9-induced osteogenic differentiation of MSCs, and will provide a theoretical and experimental basis for the use of BMP9 in clinical treatment of fracture and bone defect in the future.