CaV1.2调控牙髓损伤修复的分子机制研究

CaV1.2在调控牙髓干细胞（DPSC）成牙和成神经分化过程中，具有必不可少的重要作用。以往研究CaV1.2通路对DPSC分化的影响，大多基于对钙离子通道的负向调控而进行的表征性研究，虽已证实其在参与DPSC分化过程中的必要性，但尚未明确CaV1.2调节受损牙髓修复的分子机制，从而限制了临床开发修复牙髓相关新药的研究。本项目基于牙髓受损模型，以激动调控为导向，重点研究正向调控CaV1.2对DPSC成牙向和成神经向分化的作用机制；通过分析CaV1.2蛋白质的三维构象，探究激动小分子与CaV1.2的结合模式，获取对接信息，建立工作框架，设计开发小分子药物；利用牙髓受损模型，验证新药修复受损牙髓的潜能。项目实施将明确CaV1.2修复受损牙髓的分子机制，指导开发新药，推动临床转化，为未来临床修复受损牙髓提供新途径。

CaV1.2 plays an indispensable and important role in the regulation of dental pulp stem cell (DPSC) odontogenic and neurogenic differentiation. Previous studies of CaV1.2 pathway on DPSC differentiation are mostly phenomenon studies based on the negative regulation of calcium ion channels. Although the necessity of CaV1.2 in DPSC differentiation has been confirmed, the molecular mechanism of it has not yet been clarified. Therefore, it has limited the clinical development of new drugs for dental pulp repair. This project is based on the dental pulp injury model, focusing on activation regulation, to study how CaV1.2 regulates DPSC odontogenic and neurogenic differentiation processes. By analyzing the three-dimensional structure of CaV1.2 protein, we explore the combining mode between small molecular agonist and CaV1.2 protein to obtain docking information, aiming to establish a working framework which is guiding the design and development of small molecular drugs. Finally, we will use injury model of dental pulp to verify the potential of new drugs in repair. The implementation of this project will clarify the molecular mechanism of CaV1.2 to repair injury dental pulp, guide the development of new drugs, promote clinical transformation, and provide a new way to therapy damaged dental pulp in the future.