Dentino-enamel junction genetic-structural correlation

描述：(申请人提供)牙齿是按等级组织的 由外胚层衍生的釉质和外胚层组成的结构 衍生牙本质通过牙本质-牙釉质连接处(DEJ)结合。值得注意的是，美国司法部 坚固地结合坚硬易碎的牙釉质和灵活坚韧的牙本质，因为 不同的材料通常会集中应力并分层。釉质 提供坚硬、耐磨和耐酸的咀嚼表面，而牙本质 吸收能量，抗骨折。因此，牙齿的成功与否取决于 在美国司法部。虽然关于牙齿形成的遗传学有很多新的知识 已经变得可用的，对结构的知识已经落后了。我们提出了一个 一系列实验，使用最常见的蛋白质中的设计扰动 在牙釉质和牙本质基质中，釉原蛋白和I型胶原分别在 转基因小鼠，阐明DEJ的遗传-结构-功能 两性关系。我们预测，釉原蛋白组装基序的移除将 阻止正常的釉原蛋白自组装，导致大量釉质缺陷和 作为DEJ缺陷。使用I型胶原缺陷小鼠，我们预测两者 会产生牙本质和DEJ缺陷，因为不仅会形成牙釉质 针对有缺陷的牙本质基质凹陷，但胶原蛋白可能有直接的 在DES处连接牙本质和牙釉质的结构作用。我们预测， 缺陷将使用断裂力学和成像技术进行识别。 DEJ的失效模式将被识别并与特定的蛋白质和 他们的基因。DES用来避免灾难性破坏的策略将 被刻画出来。已定义的遗传缺陷将与特定的结构相关 结果。具体目标是：1)测量和比较牙釉质断裂 正常野生型小鼠的三维韧性和硬度 转基因釉原蛋白自组装缺陷小鼠；2)测量和比较 正常野生型小鼠牙本质硬度与转基因I型胶原的比较 3)测定和比较DEJ界面断裂韧性和 正常野生型小鼠的DES失败机制；与转基因小鼠的DES失败机制 釉原蛋白自组装缺陷小鼠和I型胶原缺陷小鼠。 最终，这项工作将允许特定动物的未来发展 影响人类的遗传性釉质缺陷模型；允许更好的仿生 人工修复体和牙本质之间的接口有待设计；以及 人工组织工程化的DEJ。

DESCRIPTION: (provided by applicant) Teeth are hierarchically organized structures consisting of ectodermally derived enamel and ectomesenchyntally derived dentin united by the dentino-enamel junction (DEJ). Remarkably, the DEJ robustly unites stiff brittle enamel with flexible tough dentin, because dissimilar materials usually concentrate stresses and delaminate. Enamel provides a hard, wear and acid resistant masticatory surface, whereas dentin absorbs energy and resists fracture. Thus the success of teeth is dependent upon the DEJ. Although much new knowledge on the genetics of tooth formation has become available, knowledge of structure has lagged behind. We propose a series of experiments, using designed perturbations in the commonest proteins in enamel and dentin matrices, amelogenin and type I collagen respectively in transgenic mice, to elucidate the DEJs genetic-structural-functional relationships. We predict that removal of the amelogenin assembly motifs will prevent normal amelogenin self-assembly, producing both bulk enamel defects and as DEJ defects. Using a type I collagen defect mouse we predict that both dentin and DEJ defects will be produced, because not only will enamel form against a defective dentin matrix intaglio, but that collagen may have a direct structural action bridging dentin to enamel at the DES. We predict that the defects will be identifiable using fracture mechanics and imaging techniques. Failure modes of the DEJ will be identified and linked to specific proteins and their genes. Strategies utilized by the DES to avoid catastrophic damage will be characterized. Defined genetic defects will be linked to specific structural outcomes. Specific aims are: 1) To measure and compare enamel fracture toughness and hardness in three dimensions of normal wild type mice to that of the transgenic amelogenin self assembly defect mice; 2) To measure and compare dentin hardness in normal wild type mice to that of transgenic type I collagen defect mice; 3) To measure and compare DEJ interfacial fracture toughness and DES failure mechanisms in normal wild type mice; with those in transgenic amelogenin self assembly defect mice, and type I collagen defect mice. Ultimately, this work will permit the future development of specific animal models of inherited enamel defects that affect humans; allow better biomimetic interfaces between artificial restorations and dentin to be designed; and lead to an artificial tissue-engineered DEJ.