SSUH2基因调节牙齿发育及矿化的作用机制研究

我们首次报道了导致牙本质发育不良I型的致病新基因SSUH2，研究发现SSUH2基因变异影响了牙齿的发育及牙本质矿化，进一步研究提示其通过DSPP相关信号通路以及与COL2A1、COL10A1等因子协同参与牙齿发育及牙本质矿化的调控。但是，SSUH2是如何与DSPP相关信号通路及COL2A1、COL10A1等因子相互关联调节牙齿发育及矿化的机制还需深入研究。在本研究中，我们拟通过构建稳定表达SSUH2基因成牙本质细胞株、SSUH2基因敲除小鼠，通过蛋白互作、信号通路分析及牙髓干细胞培养分化等研究，来明确SSUH2基因与DSPP相关信号通路、COL2A1和COL10A1等因子在牙齿发育及矿化过程中的协同作用，探索发现与SSUH2基因相关的新的牙齿发育及矿化调控分子信号通路。研究结果将为牙齿的发育尤其是牙本质细胞的分化和矿化提供新的分子机理，为牙齿发育相关疾病的诊治提供新的理论依据和研究新靶点。

Our previous studies have identified SSUH2 as a new pathogenic gene for dentin dysplasia I. Our study have shown that the defect of SSUH2 gene to affect the dentinal development and tooth mineralization. Further investigation suggested that SSUH2 might be associated with DSPP signaling pathway or COL2A1, COL10A1 gene to regulate the tooth development and mineralization. However, the mechanisms of the interaction between SSUH2 and other proteins including DSPP, COL2A1, and COL10A1 need to be further studied. In this study, we plan to elucidate the molecular mechanism of SSUH2 gene regulating tooth development and mineralization by interacting with DSPP and other signal pathway through in vitro protein-protein interaction studies, signal pathways analysis, and dental pulp stem cell culturing with Ssuh2 gene knock-out mouse. The understanding of molecular mechanisms of tooth development regulated by SSUH2 gene will bring us more information about the development or mineralization of tooth, which may provide new theoretical basis and research targets in the diagnosis, treatment and prevention of diseases related to the development of tooth.