Formation of the Enamel-Dentin Interface

描述（由申请人提供）：牙齿的两个主要矿化组织，即坚硬易碎的釉质和较软且更具弹性的牙本质，通过称为牙本质-釉质连接（DEJ）的独特界面连接在一起。尽管它们的结构、组成和机械性能存在巨大差异，但这两种组织通常可以一起工作数十年而不会出现重大故障，考虑到它们不会重塑的事实，这尤其令人惊讶。然而，在患有由主要牙齿蛋白质突变引起的疾病的患者中，这两种组织之间的界面受到损害，这通常表现为牙本质和釉质层的分层。这些数据表明，这些基质蛋白是必不可少的元素，有助于机械弹性的DEJ。具体来说，我们认为这些蛋白质调节界面处的矿物质形成和结构组织，并有助于成熟牙齿中DEJ的增韧。为了验证这一假设，我们建议进行一项全面的研究，在体内和体外的方法。我们在目标1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该界面的形成和组织; 目标二：研究体外模型系统中牙本质和釉质蛋白复合物控制矿物质形成的机制;目的3：通过研究缺乏主要牙齿蛋白的KO动物中的裂纹扩展，研究牙本质和釉质的主要蛋白在DEJ增韧中的作用。我们期望这种理解将大大有利于临床牙科提供新的治疗程序和提高冠修复的质量和寿命的科学依据。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.