本课题组前期研究发现在成牙本质细胞分化及修复性牙本质形成过程中有自噬-溶酶体途径活化。我们提出假说："自噬参与了成牙本质细胞分化及损伤修复过程"。本项目将利用体外成牙本质细胞样细胞系诱导分化模型、LPS刺激成牙本质细胞样细胞系炎症损伤模型，牙胚器官培养及构建在成牙本质细胞中特异性敲除重要自噬基因的条件性基因敲除鼠等手段，旨在进一步研究：(1)自噬-溶酶体相关基因与成牙本质细胞分化基因表达的相关性；(2) 利用特异性自噬阻断剂或诱导剂，明确自噬对成牙本质细胞分化及损伤修复的调控作用；(3) 利用RNAi抑制p62和TFEB、PCR Array、Antibody Array等技术，明确核心自噬调控通路p62/mTOR/TFEB/TFE3/TGFβ1在成牙本质细胞分化及损伤修复过程中的作用和分子机制。该项研究将有助于加深对成牙本质细胞分化及修复性牙本质形成的理解。

Our pilot study suggested that autophagy, an autophagosome-lysosome mediated protein-degradation process, was significantly activated in odontoblast differentiation and reparative dentin formation. We hypothesized that autophagy might participate in odontoblast differentiation and reparative dentin formation. In this project, we try to delinate our hypothesis using in vitro and in vivo models such as odontoblast like cells induction and differentiation assay in vitro, ex-vivo tooth germ organ culture, and dentin-specific autophagy related gene knockout mouse model. We will focus on: (1) the expression of autophagy related genes and proteins during odontoblast differentiation and reparative dentin formation. And its relationship with odontoblast differentiation genes and proteins; (2) the biological role of autophagy during odontoblast differentiation and reparative dentin formation; (3)the core machinary of p62/mTOR/TFEB/TFE3/TGFβ1 regulating autophagy in odontoblast differentiation and reparative dentin formation. The achievements of this project will enforce the interpretation of the regulation of odontoblast differentiation and reparative dentin formation.