RhoA/ROCK/PTEN信号通路在牙髓缺损修复中的分子机制研究

Pulp inflammation caused by bacterial infection is one of common oral diseases.The main traditional method for treating pulp inflammation is root canal treatment.Although it has good biological compatibility for root canal filling and can seal apical effectively, teeth will losenutrition metabolism after root canal treatment and still can not replace the pulp tissue with normal function.Tissue engineering and regenerative medicine technique has been made a breakthrough of the traditional root canal treatment. It is a new techinique to sow and cultivate functional dental pulp stem cells on the scaffolds to attach, proliferate in vitro and graft into the body to restore defective dental pulp. However, the study of dental pulp cells adhesion, proliferation, differentiation, migration is not very mature. Previous reports has investigated that Ras homologous gene family member A (RhoA), Rho related kinase (ROCK), phosphatase and tensin homolog (PTEN) and Ras related C3 botulinum toxin substrate 1 (Rac1) are associated with cell adhesion, proliferation and motility. Therefore, this project will be aimed at using pharmacological method to overcome defective cell signaling to promote dental pulp regeneration and pulp repair.

细菌感染、外伤等引起的牙髓炎症是常见的口腔疾病之一。对于牙髓炎症疾病主要的治疗方法是对患牙进行根管治疗,但是经过根管治疗的牙齿依然无法替代有正常功能的牙髓组织。随着组织工程与再生医学技术的迅猛发展，以生物学组织工程为基础，设计替代损伤的牙髓组织进行牙髓再生，其主要目标是牙本质的再生和牙髓正常活力的恢复。尽管这些基础研究工作日益增多，真正报道疏水性支架材料上牙髓组织再生相关的细胞附着、增殖、移动、分化等信号传导研究较少。据研究报道，Ras同源基因家族成员A（RhoA）,Rho相关激酶 (ROCK),磷酸酶和张力蛋白同源（PTEN）以及Ras相关C3肉毒杆菌霉素底物1（Rac1）等信号分子与细胞黏附有关，并具有调节细胞黏附、增殖、移动的功能。为此，本项目将利用牙髓干细胞在模仿疏水性支架材料上研究细胞附着、增殖、移动以及分化等相关信号传导，用信号传导为更好地牙髓再生奠定坚实的理论基础。

随着现代根管治疗的迅猛发展，牙髓再生治疗在牙体牙髓病学中受很大重视。目前所谓牙髓再生就是牙髓学运重建，而真正的牙髓再生仍处于研究阶段。本项目针对牙髓再生做了一定的基础研究。在牙髓再生所需的代表疏水性支架材料的表面上研究牙髓干细胞的附着、增殖、分化等生物活性，并且研究参与这些细胞活性的RhoA、ROCK、PTEN等信号分子及其它们之间的关系，找出信号传导缺陷，利用抑制剂以生物模式克服信号传导缺陷，为更好的牙髓再生奠定坚实的理论基础。