DNA双链断裂修复蛋白XRCC2调控牙髓干细胞成牙本质向分化的机制探究

龋病及牙髓病是口腔临床最常见的牙体硬组织和/或软组织破坏性疾病。其中牙齿轻微损伤可促进牙髓干细胞分化成牙本质细胞，进而形成修复性牙本质。目前认为DNA损伤修复缺陷与细胞的分化相关，但具体机制尚不清楚。XRCC2作为DNA双链断裂修复蛋白，在多种组织细胞生理病理过程中发挥重要作用。我们前期研究发现人牙髓干细胞成牙本质向分化过程中XRCC2表达增加，且敲低XRCC2抑制细胞DSP、DMP-1的表达，提示该因子在牙髓干细胞成牙本质向分化过程中发挥作用，但作用机制尚不清楚。本项目拟在前期工作的基础上，建立修复性牙本质形成小鼠模型及异位牙髓再生裸鼠模型，并通过改变细胞中XRCC2的表达，结合分子生物学和生物信息学技术，探究XRCC2对牙髓干细胞成牙本质向分化的动态调控作用及分子机制。扩展外界因素结合细胞内在缺陷对牙髓功能损坏机制的理解，为临床牙体疾病防治方法以及牙髓再生治疗提供新的思路和理论基础。

Dental caries and dental pulpitis are the most common diseases with the destruction of dental hard and/or soft tissues. When the teeth suffer from caries or mild stimulus, the dental pulp stem cell（DPSC）will differentiate into odontoblasts, then the odontoblasts will mineralize into mature, and then form reparative dentin. The defect of DNA damage repair was reported to be related to cell differentiation, but the mechanism has been unknown. XRCC2 is a DNA damage repair protein and plays an important role in the physiological and pathological processes of multiple tissue cells. Our previous studies showed that the expression levels of XRCC2 increased in odontoblastic differentiation DPSC and XRCC2 knockdown in DPSC inhibited the expression levels of DSP and DMP-1, suggesting that XRCC2 might play a role in the process of DPSC odontoblastic differentiation. However, the specific molecular mechanism remains unclear. This study aims to explore the dynamic functions of XRCC2 in regulation of DPSC odontoblastic differentiation by a variety of molecular biological methods and the establishment of reparative dentin formation mouse models. This study will help to reveal the role of DNA damage and XRCC2 in the odontoblastic differentiation process of DPSC, expand the understanding of the mechanism of dental pulp damage caused by external factors and intracellular defects, at the same time, provide new ideas and theoretical basis for prevention and treatment methods of dental caries and pulpal diseases.