在牙齿发育过程中骨形态发生蛋白、Wnt、成纤维细胞生长因子、音猬因子信号通路的作用及机制

Molecular mechanisms of bone morphogenetic protein, Wnt, fibroblast growth factor and sonic hedgehog signaling pathways in tooth development

背景:牙齿发育过程中,多种通路在上皮-间充质间传递信息,共同调控细胞的增殖、分化、迁移、存活和凋亡。其中主要为骨形态发生蛋白、成纤维细胞生长因子、Wnt、音猬因子通路。目的:对牙齿发育过程中骨形态发生蛋白、成纤维细胞生长因子、Wnt、音猬因子4种主要信号通路研究进展做一综述,为干细胞牙向分化研究提供参考。方法:由第一作者通过中国知网检索平台和PubMed数据库检索所需文献。检索时间为2004年至2017年,检索关键词分别为"骨形态发生蛋白,成纤维细胞生长因子,Wnt,音猬因子,牙齿发育,牙发生""Bone morphogeneticprotein, Fibroblastgrowthfactorpathway, Wntprotein, Sonichedgehog, Tooth development,Toothorganogenesis"。纳入与牙齿发育骨形态发生蛋白、成纤维细胞生长因子、Wnt、音猬因子信号通路相关的研究,选择近期发表且内容描述详实、严谨,观点明确的文章。结果与结论:骨形态发生蛋白、成纤维细胞生长因子、Wnt、音猬因子信号通路作用范围广,几乎涵盖了牙胚发育起始、形态发生及细胞分化等各个方面。此外,4种信号通路间联系紧密,彼此促进、相互制约,构成一复杂的网络。拮抗因子的逆向调控机制是该网络的重要组成部分,对牙齿最终准确形成至关重要。

BACKGROUND:During the development of teeth,several signaling pathways,such as bone morphogenetic protein(BMP),fibroblast growth factor(FGF),Wnt,and sonic hedgehog(Shh)signaling pathways,transmit message between epithelium and mesenchyme.These mediators are required for cell division,differentiation,migration,survival and apoptosis.OBJECTIVE:To review how the BMP,FGF,Wnt,and Shh signaling pathways regulate tooth development in order to provide reference for the study on stem cell differentiation into odontogenic cells.METHODS:Articles were retrieved from CNKI and PubMed database(from 2004 to 2017)with the key words of“bone morphogenetic protein,fibroblast growth factor pathway,Wnt protein,sonic hedgehog,tooth development,tooth organogenesis”.Studies related to molecular mechanisms of BMP,FGF,Wnt,Shh signaling pathway in tooth development and the recent articles with detailed,rigorous content as well as unambiguous viewpoint were included.RESULTS AND CONCLUSION:The BMP,FGF,Wnt,and Shh signaling pathways are the pivotal molecular cascades throughout the whole stage of tooth development,regulating initiation,morphogenesis and cytodifferentiation of dental germ.Moreover,the four signaling pathways are closely related,promoting and restricting each other,and form a complex network.The reverse control mechanism of antagonistic factor is an important part of the network,which is critical to the terminal pattern and amount of the teeth.