Formation of the Enamel-Dentin Interface

描述(申请人提供)：拟议研究的目的是提高我们对牙釉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了解。釉质矿化始于一层矿化牙本质的表面，这可能在初期釉质的形成中起着重要作用。牙本质和牙釉质是两种矿化组织，具有截然不同的力学和结构特性，通常联合运行数十年，没有失败。如此出色的机械耐力需要这两种组织之间非常牢固的结合。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。对于组织修复来说，界面稳定性的问题也是非常重要的，在组织修复中，由于组织和修复材料之间的弱界面，经常会发生植入失败。在初始矿化过程中，牙本质和牙釉质组织之间的相互作用很可能对这一至关重要的界面的正确形成起着重要作用。我们假设在牙釉质和牙本质之间的分界处开始矿化是一个高度整合和专业化的过程，对于这个机械上坚固的分界的正确形成是必不可少的。我们还假设，在这个界面上最初形成釉质的机制与釉质发生的其他阶段不同。我们已经确定了三个主要因素来区分初期釉质形成和后期釉质形成：1)在最初釉质形成部位存在牙本质矿物；2)存在瞬时矿物相；以及3)在最初釉质形成部位存在独特的大分子组成。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的研究，以更好地了解牙釉质初始形成的基本机制。具体地说，我们在目标1中提出：研究牙本质和釉质晶体在初始釉质矿化部位的相互作用，特别是牙本质和釉质晶体之间的外延关系；目标2：研究瞬时无定形矿物相在釉质形成初期的作用；以及目标3：在一系列体外矿化实验中，研究初始釉质矿化部位的大分子组成，特别是蛋白质-矿物相互作用，并阐明这些大分子和超分子集合体在初始釉质形成中的可能作用。我们希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了解，这将有望导致新的先进材料和/或矿化组织修复程序的开发。

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.