【作者】 赵征；

【导师】 文玲英； 金岩；

【作者基本信息】 第四军医大学 ， 口腔临床医学， 2006， 博士

【摘要】 牙齿发育是两种相邻组织一外胚上皮和神经嵴来源的间充质相互作用的结果，呈时空变化的基因调控在牙胚发育过程中发挥关键作用，调节细胞的增殖、分化和凋亡，决定牙胚的发育进程。金属蛋白酶解离素28(adisintegrin and metalloproteinase 28，ADAM28)是ADAM家族中的新成员，是定位于细胞膜且具备自身催化活性的分泌型糖蛋白，是前期我科采用改良消减杂交技术从先天性牙根发育不良患儿的差异表达基因中筛选出来的牙齿、牙根发育相关基因。ADAM28在诸多生理过程中起着重要作用：参与细胞增殖、分化，胞外基质重建、血管形成和细胞迁移等。但是，目前尚无有关ADAM28与牙齿发育关系的研究报道。 本课题的研究目的是从转录、翻译和蛋白水平探讨ADAM28在牙胚发育过程中的时空分布特点及对牙源性间充质细胞增殖、分化、凋亡等生物学特性的影响，并从中分析它可能的作用机制，为今后对ADAM28功能的深入研究提供可靠的实验和理论依据。 本课题采用组织学、免疫组织化学、细胞培养、基因重组、基因转染、ELISA、Western blot、RT-PCR、反义核酸等技术方法进行了以下四部分实验研究，主要研究内容和结果如下： 第一部分 采用组织学方法观察到小鼠下颌第一磨牙牙胚从蕾状期到牙根形成期的发育时序及形态特点。应用免疫组织化学方法检测到BSP、OPN、DSPP、更多还原

【Abstract】 Teeth develop as a result of the interactions between ectoderm epithelia and mesenchyme from neural crest. Gene regulation with spatiotemporal changes play an important role in the course of tooth germ development such as regulating cell proliferation, differentiation and apoptosis and determine the developmental process of tooth germ. ADAM28 is a newly discovered member of a disintegrin and metalloproteinase (ADAM) family, and it is also a secretion type glycoprotein located in cellular membrane with autocatalytic activity. ADAM28, which is considered as a gene related to tooth and tooth root growth, is screened by improved differential hybridization from differential expression genes of children suffering from congenital hypoplasia of tooth root. ADAM28 plays an important role in various physiological processes such as cell proliferation, differentiation, extracellular matrix reconstruction, vasiformation and cell migration. However, there has not been reported about the relationship between ADAM28 and tooth development.Based on the transcription, translation and protein levels, this study is aimed to investigate the spatiotemporal distribution features of ADAM28 during tooth germ development and its effects on the proliferation, differentiation and apoptosis of odontogenic mesenchymal cells and to analyze its possible更多还原