TGF-β1/EGR2信号通路在牙髓干细胞成牙分化及生物牙根再生中的作用和机制研究

构建生物牙根的组织工程技术手段是目前较为可行的牙再生策略，然而生物牙根再生的关键在于如何定向调控干细胞成牙分化。前期研究发现，处理牙本质基质（Treated dentin matrix，TDM）是诱导细胞成牙分化和实现生物牙根再生的理想模型。项目组首次阐明了TDM的蛋白组，并发现TDM诱导人牙髓干细胞成牙分化时早期生长应答因子2（Early growth response 2，EGR2）表达显著上调，但其具体作用和表达调控机制尚不清楚。根据生物信息分析等实验结果认为可能与TDM中含量丰富的TGF-β1有关。本研究拟以TDM为诱导微环境，以EGR2为切入点，研究其在牙髓干细胞成牙分化中的作用，重点探讨其转录调控机制，并研究其在牙根发育及再生中的功能。本研究将为定向调控干细胞成牙分化提供实验基础，为生物牙根成功率的提高提供理论依据。

Tissue engineering techniques based biological tooth roots construction is currently a more feasible tooth regeneration strategies. However, the key to biological tooth root regeneration lies in how to commit stem cells into odontogenic lineage. Previous studies have found that treated dentin matrix (TDM) is an ideal model for inducing odontogenic differentiation and achieving biological root regeneration. Our group clarified the proteome of TDM for the first time and found that the expression of early growth response 2 (EGR2) was significantly up-regulated when TDM induced human dental pulp stem cells to differentiate into odontogenic lineage. However, the specific role and expression regulation mechanism of EGR2 are not clear. According to experimental results such as bioinformatics analysis, it may be related to the rich TGF-β1 in TDM. This study aims to use TDM as the induction microenvironment, to explore the molecular mechanism of odontogenic differentiation with EGR2 as the entry point in dental pulp stem cells. This study focus on the transcriptional regulation mechanism of EGR2, as well as to explore its function in tooth root development and regeneration. This study will provide an experimental basis for the targeted regulation of odontogenic differentiation of stem cells, and provide a theoretical basis for improving the success rate of biological tooth root.