肥大软骨细胞转分化现象的发现改写了人们对软骨内成骨的认识，然而决定肥大软骨细胞命运的细胞和分子机制一无所知。种种迹象提示细胞自噬与肥大软骨细胞的命运关系密切。转运必需内体分选复合物（ESCRT）通过多囊泡体的形成参与细胞自噬。我们前期的研究构建了在软骨细胞和肥大软骨细胞中特异性敲除ESCRT复合体重要组分Hgs的小鼠模型，发现基因敲除小鼠软骨内成骨异常，肥大软骨细胞向其他类型基质细胞的转变受到了明显的阻滞。本研究拟利用多种基于Cre-LoxP系统建立的细胞谱系示踪及基因功能验证体系，深入研究ESCRT调节的自噬在肥大软骨细胞命运决定中的机制，进而更新我们对软骨内成骨的理解和认识。

Conventional wisdom of endochondral ossification has been greatly challenged by the findings of multiple fates of hypertrophic chondrocytes. However, the cellular and molecular mechanisms underlying the fate determination of hypertrophic chondrocytes remain completely unknown. Lines of clues suggest that autophagy is tightly associated with the fate of hypertrophic chondrocytes. Functions of endosomal sorting complex required for transport (ESCRT) complexes are involved in control of autophagy by multivesicular bodies formation. Our previous studies have established multiple genetic mouse models in which the key component of ESCRT complexes Hgs was deleted specifically in growth plate chondrocytes and hypertrophic chondrocytes. Interestingly, the endochondral ossification as well as the conversion of hypertrophic chondrocytes into other types of stromal cells were greatly hampered in mutant mice. In this study, we will employ these unique mouse models to in-depth study the mechanisms underlying the essential role of ESCRT-regulated autophagy in fate determination of hypertrophic chondrocytes, and thus conceptually renew our knowledge of endochondral ossification.