Novel proteins of the enamel gene cluster: implications for biomineralization

牙釉质是人体内最坚硬的物质。它主要由羟基磷灰石（HA）组成，羟基磷灰石是一种特殊形式的磷酸钙矿物。牙釉质中的HA晶体以高度有序的方式排列，因此牙釉质不仅具有非凡的硬度，而且具有抗弯强度。牙釉质的综合机械和化学特性使其成为一种上级生物材料，其设计在恒定的机械应力、温度和pH值变化以及暴露于口腔细菌的情况下，如果适当地形成和护理，其寿命可以持续。釉质的精细结构显示出四个不同的层：初始釉质、体釉质、外釉质和表面釉质。这四个层的结构是不同的，但不知道是什么决定了它们之间的过渡。虽然已经确定了几种蛋白质，并在大量釉质的背景下进行了研究，导致表面釉质形成的机制知之甚少。然而，表面釉质是口腔微生物粘附的关键界面，这是牙齿侵蚀和腐烂（例如龋齿）的初始步骤。我们以前已经确定了一种新的蛋白质，我们已经命名为amelotin（AMTN），在外层的釉质，并显示在各种小鼠模型中，AMTN是一个可能的调节这种釉质表面结构。在这个提议中，我们建议进行实验来确定AMTN是否以及如何影响羟基磷灰石晶体的生长和结构，以及AMTN是否可以帮助再生提取的人类牙齿中的釉质表面结构。人类基因组中AMTN基因所在的区域包含其他釉质基因，但也有几个未知的基因。这些新基因的表达也将在本提案中进行研究，并将测试相关基因产物调节釉质生物矿化的能力。这项研究有望提高我们对基本生物矿化机制的理解，并可能导致保护牙齿表面免受蛀牙和侵蚀的新策略的发展。它还可能为新型生物材料的设计带来新技术。

Dental enamel is the hardest substance in humans. It consists mainly of hydroxyapatite (HA), a specialized form of calcium phosphate mineral. The crystals of HA in enamel are arranged in a highly ordered fashion, so that enamel does not only have extraordinary hardness, but also flexural strength. The combined mechanical and chemical properties of enamel make it a superior biomaterial that is designed to last a lifetime - if properly formed and cared for - under constant mechanical stress, temperature and pH changes as well as exposure to oral bacteria. The fine structure of enamel reveals four distinct layers: initial, bulk, outer and surface enamel. The structures of these four layers are distinct, but it is not known what determines the transition between them. Although several proteins have been identified and studied in the context of bulk enamel, the mechanisms that lead to surface enamel formation are poorly understood. Surface enamel , however, is the critical interface for the adherence of oral microorganisms, which is the initial step for tooth erosion and decay (e.g. caries). We have previously identified a novel protein, which we have named amelotin (AMTN), in the outer layer of enamel and shown in various mouse models that AMTN is a likely regulator fo this enamel surface structure. In this proposal we suggest experiments to determine if and how AMTN influences the growth and structure of hydroxyapatite crystals, and whether AMTN can help regenerate the enamel surface structure in extracted human teeth. The region in the human genome where the AMTN gene is located contains other enamel genes, but also several uncharacterized genes. The expression of these novel genes will also be studied in this proposal, and relevant gene products will be tested for their ability to modulate enamel biomineralization. This research is expected to improve our understanding of basic biomineralization mechanisms and may lead to the development of novel strategies to protect the tooth surface from decay and erosion. It may also lead to new technologies for the design of novel biomaterials.