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: 7745725
• 负责人: Megan Kardon Pugach
• 金额: $ 5.13万
• 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 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7745725
• 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）：适当的釉质形成需要结构基质蛋白和蛋白酶沿着矿化的协调分泌，以形成体内最坚硬和矿化最多的组织。釉原蛋白占成釉细胞分泌的有机基质的90%，并且是釉质矿化所需的。釉原蛋白的突变导致成釉不全（Al），这是一种导致釉质缺陷的遗传疾病。釉原蛋白的不同区域负责釉质矿化过程的不同方面。在釉质形成过程中，釉原蛋白由成釉细胞分泌的蛋白水解酶加工，如MMP 20。釉原蛋白的C-末端被认为是正确形成和组装纳米球、引导矿物晶体生长的球形蛋白聚集体以及与羟基磷灰石矿物相互作用所必需的。为了使用转基因和釉原蛋白缺失小鼠来检查釉原蛋白C-末端在釉质结构完整性中的作用，本提案将：1）确定缺少釉原蛋白C-末端对釉质微观结构和纳米机械性能的影响; 2）确定MMP 20在C-末端加工釉原蛋白对釉质微观结构、纳米机械性质和有机基质去除的重要性;和3）检查具有釉原蛋白C-末端突变的小鼠的视杆组织和成釉细胞Tomes'突起形态。 公共卫生关系：这项研究将有助于目前的知识釉基质蛋白在釉质发育和矿化的作用。分析釉原蛋白和其他釉基质基因突变的转基因小鼠模型可以增加对患者不同Al表型及其相应基因突变的理解。因此，可以改善患有Al和其他釉质疾病的人的临床治疗和方法。