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

基本信息

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
项目类别：
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

项目摘要

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.

项目概要/摘要牙釉质由成釉细胞在两个主要阶段形成：分泌阶段和成熟阶段，每个阶段的细胞阶段在功能上是不同的。牙釉质的体积（厚度）是在分泌阶段形成的，然后在成熟阶段通过增加离子传输而矿化。流程失调定义任一阶段都会导致牙科疾病。牙釉质的形成是最常见的研究通过分析牙釉质基质蛋白和蛋白酶的作用。方法论的进步，一些 PI 实验室开发的技术以及牙釉质生物学与其他学科的不断整合，提供了一个解决牙釉质细胞生理学和代谢关键方面的平台矿化和牙齿疾病。该拨款提案将确定牙釉质中的新分子途径通过将 Ca2+ 稳态与氧化还原环境和线粒体功能联系起来来形成。要做的事为此，我们将在其他系统中使用缺乏 Ca2+ 流入的小鼠模型和缺乏 Ca2+ 流入的小鼠线粒体 Ca2+ 摄取。线粒体和氧化还原在信号传导和代谢中的作用牙釉质的形成目前尚不清楚。