力学刺激对骺板生长发育及骨骺干细胞的代谢活动有重要影响，阐明骨骺干细胞力学信号转导过程对于早期治疗和及时干预骨骺发育障碍十分关键。申请者在前期的研究中发现动态应力刺激能够促进骨骺干细胞YAP蛋白去磷酸化并促进其直接调控靶基因CTGF和ANKRD1表达上调。本项目拟进一步阐明Hippo-YAP通路上游关键位点FA在力学干预调控YAP中的作用，肌动蛋白CSK及微管蛋白CSK对YAP的调节作用。在此基础上进一步研究Hippo通路中核心激酶MST1/2与LATS1/2在力学干预及CSK调控YAP中的作用和机制，分析探讨力学干预调控YAP活性的作用靶点。最后调控力学干预下Hippo-YAP通路关键激酶的活性并研究此通路与细胞分化/凋亡间的关联。深入研究Hippo-YAP通路在骨骺干细胞力学信号转导中的作用与机制，可为骨骺发育障碍疾病的早期治疗与及时干预提供新的理论基础与实验依据。

Mechanical stimulation plays an important role in the growth/development of the growth plate and metabolism of the precartilaginous stem cells. Clarifying the mechanotransduction process of precartilaginous stem cells is critical for the early treatment and timely intervention of the growth plate development disorders. In our previous studies, we found that dynamic stress could promote dephosphorylation of YAP protein and elevation of the CTGF/ANKRD1 mRNA. This study tries to elucidate the role FA plays in the regulation of YAP induced by mechanical stress, the role actin CSK and tubulin CSK plays in the regulation of YAP. This study will further elucidate the role MST1/2 and LATS1/2 play in the regulation of YAP induced by mechanical stress or regulated by CSK. Finally this study will study the relationship between Hippo-YAP signalling pathway and differentiation/apoptosis of the precartilaginous stem cells.Intensive study of the Hippo-YAP signalling pathway in the mechanotransduction process of precartilaginous stem cells will provide novel theoretical and experimental basis for the early treatment and timely intervention of the epiphyseal growth plate development disorders.