ENAMEL FLUOROSIS; MECHANISMS OF ACTION

描述（改编自研究者摘要）：牙釉质高度 由上皮成釉细胞形成的矿化硬组织， 最初作为细胞外基质分泌，含有以下物质的复杂混合物： 独特的蛋白质细胞和基质的相互作用明显得到了很好的控制， 负责牙釉质发育和生物矿化， 很好理解。摄入氟化物会干扰牙釉质的形成， 导致釉原蛋白从成熟基质中去除的延迟， 导致更多多孔的成熟釉质。本报告中提出的研究 应用程序已经从主要研究者的持续兴趣， 氟中毒的机制。在这项建议中，提出了两种可能的机制， 将测试氟斑牙，包括牙釉质的差异结合 蛋白质转化为含氟磷灰石，以及氟对 成釉细胞功能具体目的是：1）测量主要矿物 氟化人牙釉质的成分，并合成含氟 基于这些测定的碳酸化羟基磷灰石; 2）比较 釉质基质蛋白与碳酸化羟基磷灰石的相对结合 羟基磷灰石和含氟碳酸化羟基磷灰石; 3） 确定氟化物是否改变mRNA表达，蛋白质分泌，或 体外成釉细胞样细胞蛋白酶活性; 4）开发人 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牙釉质发育，以及 是形成氟牙釉质的原因

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.