软骨内成骨是骨骼发生的主要方式，但其调控机制尚未完全明确。本团队在小鼠跖骨组织中敲除Hippo信号通路支架蛋白Salvador1（Sav1）后发现，跖骨增长受限，增殖区变短，肥大区Col10a1表达下降；小鼠软骨细胞中敲除Sav1引起下游效应分子YAP的表达增强。这说明Hippo信号通路分子Sav1在软骨细胞的增殖及分化过程中发挥重要作用。然而，Sav1对软骨内成骨及骨骼形成过程的影响尚缺乏体内数据，机理也有待进一步研究。因此，本项目将建立软骨组织中Sav1特异性敲除小鼠模型，通过分析小鼠骨骼的大体及显微结构、胶原合成及修饰、Hippo-YAP/TAZ及软骨生成相关信号通路的变化，明确Sav1敲除对软骨内成骨及骨骼形成的作用，阐明Sav1调控软骨生成及稳态的分子机制，为骨骼发育异常疾病的防治提供理论基础。

Endochondral ossification is a key contributor to the development of the vertebral skeleton and its regulatory mechanisms are not yet clear. During endochondral ossification, Hippo pathway regulates chondrocyte differentiation at multiple steps through down-stream target effector YAP. Salvador1 (Sav1) is one of the core components of the Hippo pathway. .Research studies by our group have shown that the inhibition of Sav1 results in the limitation of the metatarsal growth, shortening of proliferative zone and a lower expression of Col10a1 in hypertrophy zone. Further studies found that knockdown Sav1 by siRNA in chondrocytes increases the expression of YAP. To date, the effect of Sav1 knockout in vivo has been demonstrated in a few specific organs, including the liver, skin and colon, not cartilage. .Therefore, we have generated cartilage-specific Sav1-knockout mice to explore the regulation of Sav1 on endochondral ossification. During the studies periods, the general observation is made at the different time point and collagen synthesis and mineralization is detected after euthanasia. By analyzing the differences between Sav1-knockout mice and control mice in Hippo-YAP/TAZ pathway and chondrogenesis-related signaling pathway, we have developed a regulatory cross talk between Sav1 and endochondral ossification, which may provide theoretical basis for the prevention and treatment of diseases related to skeletal dysplasia.