Formation of the Enamel-Dentin Interface

描述(申请人提供)：牙齿的两个主要矿化组织，硬而脆的牙釉质和更软、更有弹性的牙本质通过一种独特的界面连接在一起，称为牙本质-牙釉质连接点(DEJ)。尽管这两个组织在结构、成分和机械性能上存在巨大差异，但它们通常在一起运行数十年而没有发生重大故障，考虑到它们不会重塑的事实，这尤其令人惊讶。偶然地，在主要牙齿蛋白突变引起的疾病患者中，这两个组织之间的界面受损，通常表现为牙本质和釉质层的分层。这些数据表明，这些基质蛋白是促进DEJ机械弹性的基本元素。具体地说，我们认为这些蛋白质调节界面上的矿物质形成和结构组织，并有助于增韧成熟牙齿的DEJ。为了验证这一假设，我们建议使用体内和体外方法进行一项全面的研究。我们在Aim1中提出：在缺乏主要牙齿蛋白的遗传小鼠模型中研究DEJ的形成、结构和组成，以揭示它们如何控制这一界面的形成和组织； 目的2：在体外模型系统中研究牙本质和釉质蛋白复合体对矿物形成的调控机制：目的3：通过对缺主要牙蛋白的KO动物裂纹扩展的研究，研究牙本质和牙釉质主要蛋白在增韧DEJ中的作用。我们预计，这些认识将为临床牙科提供新的治疗方法的科学依据，并提高冠修复的质量和寿命。我们还希望，我们的研究结果将有助于开发具有高界面稳定性的新型智能纳米材料，用于医疗和牙科应用。

DESCRIPTION (provided by applicant): Two major mineralized tissues of a tooth, hard and brittle enamel and a softer and more elastic dentin are joined together via a unique interface called dentino-enamel junction (DEJ). Despite huge differences in their structure, composition and mechanical properties these two tissues normally perform together for tens of years without a major failure, which is especially amazing, considering the fact that they do not remodel. Improtantly, in the patients with diseases caused by mutations in major tooth proteins, the interface between these two tissues is compromised, which is often manifested by delamination of dentin and enamel layers. These data suggest that these matrix proteins are essential elements contributing to the mechanical resilience of the DEJ. Specifically we believe that these proteins regulate mineral formation and structural organization at the interface as well as contribute to the toughening to DEJ in mature teeth. To test this hypothesis we propose to conduct a comprehensive study using in vivo and in vitro approaches. We propose in Aim1: To study formation, structure and composition of the DEJ in genetic mice models lacking major tooth proteins in order to reveal how they control formation and organization of this interface; in Aim 2: To study the mechanisms of control of mineral formation by complexes of dentin and enamel proteins in an in vitro model system; and in Aim 3: To conduct studies of the roles of the major proteins of dentin and enamel, in toughening of the DEJ by studies of the crack propagation in the KO animals lacking major tooth proteins. We anticipate that such understanding will greatly benefit the clinical dentistry by providing the scientific basis for novl treatment procedures and improving quality and longevity of crown restorations. We also expect that our results of will aid in the development of novel smart nanomaterials with high interfacial stability for medical and dental applications.