ENAMEL FLUOROSIS; MECHANISMS OF ACTION

描述(改编自《调查者摘要》)：牙釉质含量高 由上皮性成釉细胞形成的矿化硬组织，是 最初以细胞外基质的形式分泌，含有复杂的 独特的蛋白质。显然细胞和基质的相互作用得到了很好的控制， 它们负责釉质的发育和生物矿化，而不是 很好理解。摄入氟化物会干扰牙釉质的形成， 导致从成熟基质中去除釉原蛋白的延迟， 导致成熟牙釉质更加疏松。在这篇文章中提出的研究 应用程序已从首席调查员对 氟中毒的发病机制。在这项提案中，有两种可能的机制 将对氟斑牙进行测试，包括牙釉质的不同结合 蛋白质对含氟磷灰石，以及氟化物的直接影响 成釉细胞功能。具体目标是：1)测定主要矿物 含氟人牙釉质的组成及含氟合成 基于这些测定的碳酸化羟基磷灰石；2)比较 釉质基质蛋白与碳化羟基磷灰石的相对结合 羟基磷灰石和含氟碳化羟基磷灰石；3)至 确定氟是否改变了mRNA的表达、蛋白质的分泌或 体外培养成釉细胞样细胞的蛋白酶活性；4)培养人 成釉细胞系。本提案中概述的目标将允许 确定氟化物如何影响发育中的牙釉质，以及 负责氟化牙釉质的形成。

DESCRIPTION (Adapted from the Investigator's Abstract): Dental enamel is highly mineralized hard tissue that is formed by the epithelial ameloblasts, and is initially secreted as extracellular matrix that contains a complex mixture of unique proteins. The apparently well-controlled cell and matrix interactions, which are responsible for enamel development and biomineralization, are not well understood. Ingestion of fluoride can interfere with enamel formation, causing a delay in the removal of amelogenin proteins from the maturing matrix, resulting in more porous mature enamel. The studies proposed in this application have evolved from the Principal Investigator's on going interest in the mechanisms of fluorosis. In this proposal, two possible mechanisms for dental fluorosis will be tested, including a differential binding of enamel proteins to fluoride containing apatite, and a direct effect of fluoride on ameloblast function. The specific aims are: 1) to measure the major mineral components of fluoride human enamel, and to synthesize fluoride-containing carbonated hydroxyapatite based on these determinations; 2) to compare the relative binding of enamel matrix proteins to hydroxyapatite, carbonated hydroxyapatite, and fluoride-containing carbonated hydroxyapatite; 3) to determine whether fluoride alters mRNA expression, protein secretion, or proteinase activity from ameloblast-like cells in vitro; 4) to develop human ameloblast cell lines. The aims outlined in this proposal will allow for determining how fluoride can affect developing enamel, and the mechanisms that are responsible for the formation of fluorosed enamel.