Formation of the Enamel-Dentin Interface

描述（由申请人提供）：本研究的目的是提高我们对牙本质初始矿化和牙本质-牙釉质界面形成的基本物理化学机制的理解。牙釉质矿化始于矿化牙本质的表面，它可能在牙釉质的初始形成中起重要作用。牙本质和牙釉质是两种矿化组织，具有截然不同的机械和结构特性，通常可以共同工作数十年而不会失效。如此出色的机械耐久性要求这两个组织之间有非常牢固的联系。对牙齿相关遗传疾病和基因敲除动物的研究表明，牙本质-牙釉质界面的正确形成对牙齿的正常功能至关重要。在组织修复中，界面稳定性的问题也非常重要，通常由于组织和修复材料之间的界面较弱而导致植入失败。在初始矿化过程中，牙本质和牙釉质组织之间的相互作用可能在这个至关重要的界面的正确形成中起着重要作用。我们假设在牙本质和牙釉质之间的边界开始矿化是一个高度整合和专业化的过程，对于这种机械坚固界面的正确形成至关重要。我们还假设，在这个界面上初始牙釉质形成的机制不同于其他阶段的成釉发育。我们已经确定了区分初始牙釉质形成和后期牙釉质形成的三个主要因素：1)牙本质矿物质在初始牙釉质形成部位的存在；2)瞬态矿物相的存在；3)在牙釉质初始形成部位有独特的大分子组成。因此，我们建议使用各种体内和体外方法对牙本质-牙釉质界面的形成进行全面研究，以更好地了解初始牙釉质形成的基本机制。具体而言，我们在目标1中提出：研究牙本质与牙釉质晶体在初始矿化部位的相互作用，重点研究牙本质与牙釉质晶体之间的外延关系；目的2：研究瞬时非晶态矿物相在牙釉质形成初期的作用；目的3：在一系列体外矿化实验中，研究初始牙釉质矿化位点的大分子组成，特别强调蛋白质-矿物质相互作用，并利用机械方法阐明这些大分子和超分子组装在初始牙釉质形成中的可能功能。我们期望这项研究的结果将提高我们对牙本质-牙釉质界面形成的基本过程的认识，这将有希望导致新的先进材料和/或矿化组织修复程序的发展。

DESCRIPTION (provided by applicant): The purpose of the proposed studies is to improve our understanding of the basic physico-chemical mechanisms of initial enamel mineralization and formation of the dentin-enamel interface. Enamel mineralization starts at the surface of a layer of mineralized dentin, which may play an important role in initial enamel formation. Dentin and enamel are two mineralized tissues with strikingly different mechanical and structural properties that normally perform jointly for tens of years, without failure. Such an outstanding mechanical endurance requires an extraordinarily strong bond between these two tissues. Studies of tooth related genetic disorders and knockout animals demonstrate that the correct formation of the dentin-enamel interface is essential for the proper tooth function. The problem of interface stability is also very important with respect to tissue repair, where often implant failure occurs due to a weak interface between tissues and repair materials. It is likely that interactions between dentin and enamel tissues during initial mineralization play an important role in the proper formation of this critically important interface. We hypothesize that the onset of mineralization at the boundary between enamel and dentin is a highly integrated and specialized process, essential for the proper formation of this mechanically robust interface. We also hypothesize that the mechanism of initial enamel formation at this interface is different from other stages of amelogenesis. We have identified three major factors that distinguish initial enamel formation from later stages of amelogenesis: 1) the presence of dentin mineral at the site of initial enamel formation; 2) the presence of transient mineral phases; and 3) a unique macromolecular composition at the site of initial enamel formation. Thus, we propose a comprehensive study of the formation of the dentin-enamel interface using a variety of in vivo and in vitro approaches to gain a better understanding of basic mechanisms of initial enamel formation. Specifically, we propose in Aim1: To study the interactions between dentin and enamel crystals at the site of initial enamel mineralization, with special emphasis on the epitaxial relationship between dentin and enamel crystals; in Aim 2: To study the role of transient amorphous mineral phases in initial stages of enamel formation; and in Aim 3: To study the macromolecular composition at the initial enamel mineralization site with special emphasis on protein-mineral interactions, and to elucidate the possible functions of these macromolecules and supra-molecular assemblies in initial enamel formation using a mechanistic approach, in a series of in vitro mineralization experiments. We expect that the results of this study will improve our knowledge of the basic processes involved in the formation of the dentin-enamel interface that will hopefully lead to the development of new advanced materials and/or procedures for mineralized tissue repair.