基于软骨内成骨的骨组织工程为大面积骨缺损的修复提供了新思路，但目前的技术路线存在软骨板退化、骨生成分布不均等问题。YAP1转录共激活因子作为细胞感受机械信号的重要效应因子，可转导生物材料的某些物理性能，如硬度，并影响MSCs向成骨、成脂和成神经细胞方向分化。鉴于成软骨细胞的同源性，我们推测通过对YAP1的作用及机制研究，可以调控MSCs向成软骨细胞方向分化、进而完成软骨内成骨。为验证这一假设，我们首先在体外检验YAP1与软骨内成骨各个阶段的相关性，其次观察YAP1在体内对转基因小鼠软骨内成骨的影响，然后探讨YAP1调控MSCs软骨向分化及肥大软骨细胞凋亡的机制，最后，通过支架设计和基因调控，了解YAP1影响MSCs软骨内成骨的效果。我们期望能够阐明YAP1对MSCs软骨向分化和肥大软骨细胞凋亡的影响及作用机制，从而有目的的调控经由软骨内成骨的组织修复过程，更有效地修复大面积骨缺损。

Bone tissue engineering based on endochondral ossification provides a new way to repair large bone defect. However, the success of this approach is hindered by core degradation and an uneven distribution of bone mineral throughout the construct. As an important sensor of mechanical signal, YAP1 (Yes-associated protein 1) transcription activation factor can convert physical characteristics of biomaterials into chemical signals to control stem cell differentiation. Considering the homology of chondroblasts to osteoblasts, lipoblasts, and neuroblasts, we hypothesize that, by studying the function and mechanism of YAP1, it can control the differentiation of MSCs into chondrocytes as well as the following endochondral ossification. To evaluate the effect of YAP1 on endochondral ossification in various stages, MSCs with enhanced or reduced YAP1 function driven by different promoters are developed in vitro, and then the conditional knockout mice are employed to investigate the function of YAP1 in endochondral ossification in vivo. Finally, through scaffold design and gene regulation, the chondrogenic differentiation of MSCs and the following endochondral ossification are observed. We expect to illuminate the mechanism of YAP1’s effect on the chondrocytes differentiation of MSCs in the early stage and the apoptosis of hypertrophic chondrocytes in the late stage. This study will provide us theoretical basis to regulate the bone tissue repair process reasonably, to promote angiogenesis more effectively, and finally to boost new bone formation in the large bone defect.