Redox and Ca2+ signaling regulation of enamel mineralization

牙釉质矿化的氧化还原和 Ca2 信号传导调节

• 批准号: 10162310
• 负责人: Rodrigo S. Lacruz
• 金额: $ 35.6万
• 依托单位: NEW YORK UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-15 至 2023-03-09
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10162310
• 关键词: Actins; Address; Affect; Ameloblasts; Amelogenesis Imperfecta; Applications Grants; Biogenesis; Biology; Cell Maturation; Cell physiology; Cells; Cellular Stress; Characteristics; Cytoskeletal Proteins; Data; Dental Enamel; Discipline; Disease; Distal; Enamel Formation; Energy Metabolism; Environment; Fluorescent Probes; Gene Expression; Gene Proteins; Genes; Genus Hippocampus; Glutathione; Homeostasis; Homologous Gene; Human; Hydrogen Peroxide; Immunofluorescence Immunologic; Immunohistochemistry; In Vitro; Ion Transport; Knockout Mice; Link; Measures; Mediating; Membrane Potentials; Metabolism; Methodology; Minerals; Mitochondria; Molecular; Monitor; Mus; Mutation; Oxidants; Oxidation-Reduction; Pathology; Pathway interactions; Peptide Hydrolases; Phenotype; Physiological; Physiology; Process; Proteins; Proteome; Reactive Oxygen Species; Regulation; Reporting; Role; STIM1 gene; Second Messenger Systems; Secretory Cell; Signal Transduction; Stress Tests; Structure; Sulfhydryl Compounds; System; Testing; Thick; Tissues; Tooth Diseases; Western Blotting; enamel matrix proteins; extracellular; in vitro Assay; innovation; mineralization; mitochondrial membrane; mitochondrial metabolism; mouse model; novel; oxidation; protein expression; sensor; tool; uptake; virtual

PROJECT SUMMARY/ABSTRACT Tooth enamel is formed by ameloblasts in two main stages, secretory and maturation, with cells of each stage being functionally distinct. The volume (thickness) of enamel is formed in the secretory stage and then mineralized in the maturation stage by increased ion transport. Dysregulation of the processes that define either stage leads to dental disease. Enamel formation has been studied most commonly by analyzing the role of enamel matrix proteins and proteases. Methodological advances, some developed in the PI's lab, and the ongoing integration of enamel biology with other disciplines, provide a platform to address key aspects of the physiology and metabolism of enamel cells in enamel mineralization and dental disease. This grant proposal will identify novel molecular pathways in enamel formation by linking Ca2+ homeostasis with the redox environment and mitochondrial function. To do this, we will use, among other systems, mouse models lacking Ca2+ influx and mice lacking mitochondrial Ca2+ uptake. The role/s of mitochondria and redox in signaling and metabolism during enamel formation are presently unknown.

项目总结/摘要 牙釉质是由成釉细胞形成的，分为两个主要阶段：分泌期和成熟期， 阶段在功能上不同。釉质的体积（厚度）在分泌期形成， 然后在成熟阶段通过增加的离子转运而矿化。过程失调 会导致牙齿疾病牙釉质的形成是最常见的研究 通过分析釉质基质蛋白和蛋白酶的作用。方法上的进步，一些 在PI的实验室开发的，以及与其他学科的牙釉质生物学的持续整合，提供 一个解决釉质中釉质细胞生理和代谢关键方面的平台 矿化和牙齿疾病。这项拨款提案将确定新的分子途径，在牙釉质 通过将Ca2+稳态与氧化还原环境和线粒体功能联系起来来形成。做 为此，我们将使用缺乏Ca2+内流的小鼠模型和缺乏Ca2+内流的小鼠模型以及缺乏Ca2+内流的小鼠模型。 线粒体钙摄取。线粒体和氧化还原在细胞内信号传导和代谢中的作用 釉质形成目前是未知的。