Song Yihua, Cao Peipei, Gu Zhifeng, Xiao Jingwen, Lian Min, Huang Dan, Xing Jing, Zhang Ye, Feng Xingmei, Wang Chenfei
1 Province Key Laboratory for Inflammation and Molecular Drug Target, Department of Stomatology, Affiliated Hospital of Nantong University, Nantong University , Nantong, China .
2 Department of Rheumatology, Affiliated Hospital of Nantong University , Nantong, China .
Cell Reprogram. 2018 Apr;20(2):117-126. doi: 10.1089/cell.2017.0041. Epub 2018 Feb 27.
Abnormal odontoblast differentiation of dental pulp stem cells (DPSCs) caused by inflammation is closely related to the development of dental caries. Neuropilin-1 (NRP1) is one of the members of neuropilin family. It can combine with disparate ligands involved in regulating cell differentiation. FYN belongs to the protein-tyrosine kinase family, which has been implicated in the control of cell growth, and the effect can be further strengthened by inflammatory factors. In our studies, we verified that NRP1 can form complexes with FYN and have the correlation changes in odontoblast differentiation of DPSCs. Therefore, we surmise that in the progress of dental caries, NRP1 interacts with FYN, by expanding inflammation and inhibition of odontoblast differentiation of DPSCs through nuclear factor kappa B (NF-κB) signaling pathway. In this subject, we first investigated the expression and interaction of NRP1 and FYN in DPSCs. And then, we researched the effect of this complex controlling downstream signal pathway in normal or inflammation stimulated DPSCs. Finally, we analyzed the relationship between this role and odontoblast differentiation of DPSCs. This research will provide the molecular mechanism of inflammation factors of dental caries through activating NF-κB signal regulating odontoblast differentiation in DPSCs for finding new potential drug targets for the clinical treatment of dental caries.
炎症引起的牙髓干细胞（DPSCs）成牙本质细胞分化异常与龋齿的发生密切相关。神经纤毛蛋白-1（NRP1）是神经纤毛蛋白家族成员之一。它能与参与调节细胞分化的不同配体结合。FYN属于蛋白酪氨酸激酶家族，其与细胞生长调控有关，且炎症因子可进一步增强这种作用。在我们的研究中，我们证实NRP1能与FYN形成复合物，并在DPSCs的成牙本质细胞分化中存在相关变化。因此，我们推测在龋齿进展过程中，NRP1通过核因子κB（NF-κB）信号通路，通过扩大炎症和抑制DPSCs的成牙本质细胞分化与FYN相互作用。在本课题中，我们首先研究了NRP1和FYN在DPSCs中的表达及相互作用。然后，我们研究了这种复合物在正常或炎症刺激的DPSCs中控制下游信号通路的作用。最后，我们分析了这种作用与DPSCs成牙本质细胞分化之间的关系。本研究将为通过激活NF-κB信号调节DPSCs成牙本质细胞分化的龋齿炎症因子分子机制提供依据，为寻找龋齿临床治疗的新潜在药物靶点提供帮助。
