The Role of the C-terminus of Amelogenen in Enamel Structure

Amelogenen C 末端在牙釉质结构中的作用

• 批准号: 8098734
• 负责人: Megan Kardon Pugach
• 金额: $ 4.23万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8098734
• 关键词: Ablation; Affinity; Ameloblasts; Amelogenesis Imperfecta; Binding; Biomechanics; C-terminal; Clinical Treatment; Defect; Dental Enamel; Deposition; Development; Dimensions; Disease; Enamel Formation; Excision; Gene Mutation; Genes; Growth; Hereditary Disease; Histologic; Human; Hydroxyapatites; Immunohistochemistry; In Situ; Knockout Mice; Knowledge; Lead; Length; Measures; Mechanics; Minerals; Morphology; Mus; Mutation; Nanosphere; Patients; Pattern; Peptide Hydrolases; Phenotype; Process; Property; Proteins; Psychological reinforcement; Regulation; Research; Role; Staging; Structure; Surface; Testing; Thick; Tissues; Tooth structure; Transgenic Mice; Transgenic Organisms; Wild Type Mouse; amelogenin; density; enamel matrix proteins; improved; mineralization; mouse model; nanomechanical; protein aggregate; public health relevance; retinal rods; tooth surface

DESCRIPTION (provided by applicant): Proper enamel formation requires coordinated secretion of both structural matrix proteins and proteases along with mineralization to form the hardest and most mineralized tissue in the body. Amelogenins constitute 90% of the organic matrix secreted by ameloblasts and are required for enamel mineralization. Mutations in amelogenin cause Amelogenesis Imperfecta (Al), which is a genetic disorder that causes enamel defects. Different regions of the amelogenin protein are responsible for varying aspects of the enamel mineralization process. Amelogenins are processed by proteolytic enzymes also secreted by ameloblasts, such as MMP20, during enamel formation. The C-terminus of amelogenin is thought to be required for proper formation and assembly of nanospheres, spherical protein aggregates that guide mineral crystal growth, and interaction with hydroxyapatite mineral. To examine the role of the C-terminus of amelogenin in enamel structural integrity using transgenic and amelogenin null mice, this proposal will: 1) determine the effect of the lack of the amelogenin C-terminus on enamel microstructure and nanomechanical properties; 2) determine the importance of MMP20 processing of amelogenin at the C-terminus on enamel microstructure, nanomechanical properties, and organic matrix removal; and 3) examine rod organization and ameloblast Tomes' process morphology in mice with an amelogenin C-terminal mutation. PUBLIC HEALTH RELEVANCE: This research will contribute to the current knowledge of the role of enamel matrix proteins in enamel development and mineralization. Analysis of transgenic mouse models with mutations in amelogenin and other enamel matrix genes can lead to increased understanding of different Al phenotypes and their corresponding genetic mutations in patients. As a result, clinical treatments and approaches for humans with Al and other enamel disorders can be improved.

描述（由申请人提供）：正确的搪瓷形成需要对结构基质蛋白和蛋白酶的协调分泌以及矿化，以形成体内最坚硬，最矿化的组织。氨基蛋白蛋白构成由成成布分泌的有机基质的90％，是搪瓷矿化所必需的。氨基蛋白蛋白的突变会引起症状不完美（AL），这是一种遗传疾病，会导致牙釉质缺陷。阿米他蛋白蛋白的不同区域负责改变搪瓷矿化过程的各个方面。氨基蛋白蛋白是由在搪瓷形成过程中由含有木材细胞（例如MMP20）分泌的蛋白水解酶处理的。氨基蛋白蛋白的C末端被认为是纳米球的适当形成和组装，指导矿物质晶体生长的球形蛋白聚集体以及与羟基磷灰石矿物质的相互作用所必需的。为了检验使用转基因和阿梅尔根蛋白null小鼠的蛋白质蛋白C末端在牙釉质结构完整性中的作用，该建议将：1）确定缺乏氨基蛋白蛋白C末端对搪瓷微结构和纳米力学特性的影响； 2）确定在C-末端对MMP20加工在搪瓷微结构，纳米力学性质和有机基质去除的重要性； 3）检查具有氨甲蛋白酶C-末端突变的小鼠中的杆组织和成纤维细胞的过程形态。 公共卫生相关性：这项研究将有助于当前对搪瓷基质蛋白在搪瓷开发和矿化中的作用的了解。分析具有氨基蛋白酶和其他牙釉质基质基因突变的转基因小鼠模型可以导致人们对不同表型及其在患者中相应的遗传突变的了解增加。结果，可以改善患有AL和其他搪瓷疾病的人类的临床治疗方法。