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Dentino-enamel junction genetic-structural correlation

牙本质-釉质连接处遗传-结构相关性

基本信息

批准号：
6946797
负责人：
SHANE NEWPORT WHITE
金额：
$ 13.5万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2002
资助国家：
美国
起止时间：
2002-08-01 至 2007-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6946797
关键词：
amelogenin atomic force microscopy collagen dental development dental structure dentin dentinogenesis functional /structural genomics gene expression genetic regulation genetically modified animals laboratory mouse protein structure function scanning electron microscopy southern blotting tooth enamel

项目摘要

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.

描述：（由申请人提供）牙齿是分层组织的由外胚层衍生的釉质和外胚层中胚层组成的结构由牙本质-釉质连接（DEJ）连接的衍生牙本质。值得注意的是，坚固地将坚硬易碎的牙釉质与柔韧坚韧的牙本质结合在一起，因为不同的材料通常集中应力并分层。釉质提供坚硬、耐磨和耐酸的咀嚼表面，而牙本质吸收能量并抵抗断裂。因此，牙齿的成功取决于在DEJ。虽然许多关于牙齿形成遗传学的新知识已经变得可用，结构的知识已经落后。我们提出了一个一系列的实验，在最常见的蛋白质中使用设计好的扰动在釉质和牙本质基质中，釉原蛋白和I型胶原分别转基因小鼠，以阐明DEJ的遗传结构功能关系。我们预测，去除釉原蛋白组装基序将阻止正常的釉原蛋白自组装，产生大量的釉质缺陷， DEJ缺陷。使用I型胶原蛋白缺陷小鼠，我们预测，牙本质和DEJ缺陷将产生，因为不仅将形成釉质，针对有缺陷的牙本质基质凹雕，但是胶原可以具有直接的在DES处连接牙本质和牙釉质的结构作用。我们预测使用断裂力学和成像技术可以识别缺陷。 DEJ的失效模式将被识别并与特定蛋白质相关联，他们的基因DES用于避免灾难性损害的策略将被定性。定义的遗传缺陷将与特定的结构性缺陷相关联。成果。具体目的是：1）测量和比较釉质破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对转基因I型胶原的硬度 3）测量和比较DEJ界面断裂韧性和正常野生型小鼠中DES失效机制;与转基因小鼠中的那些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牙本质和牙本质之间的界面设计;以及铅人工组织工程DEJ

项目成果

期刊论文数量（7）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Endodontics and tooth retention.

牙髓病和牙齿保留。

DOI：
发表时间：
2007
期刊：
The International journal of prosthodontics
影响因子：
0
作者：
White,ShaneN;Akhparyan,Elizabeth;Kutshenko,Diana;Torabinejad,Mahmoud
通讯作者：
Torabinejad,Mahmoud

Tissue mimicking materials for dental ultrasound.

用于牙科超声的组织模拟材料。

DOI：
10.1121/1.2884083
发表时间：
2008
期刊：
The Journal of the Acoustical Society of America
影响因子：
0
作者：
Singh,RahulS;Culjat,MartinO;Grundfest,WarrenS;Brown,ElliottR;White,ShaneN
通讯作者：
White,ShaneN

Penetration of radiopaque dental restorative materials using a novel ultrasound imaging system.

使用新型超声成像系统渗透不透射线的牙科修复材料。

DOI：
发表时间：
2007
期刊：
American journal of dentistry
影响因子：
1.4
作者：
Singh,RahulS;Culjat,MartinO;Cho,JasonC;Neurgaonkar,RatnakarR;Yoon,DouglasC;Grundfest,WarrenS;Brown,ElliotR;White,ShaneN
通讯作者：
White,ShaneN

Endodontics and implants, a catalog of therapeutic contrasts.

牙髓学和种植体，治疗对比目录。