Enamel biomineralization; the role of pH cycling

牙釉质生物矿化；

基本信息

批准号：
10348158
负责人：
Pamela K Den Besten
金额：
$ 50.09万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-03-07 至 2023-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10348158
关键词：
Adverse effects Affect Ameloblasts Amelogenesis Apical Bicarbonates Biocompatible Materials Calcium Calcium Channel Cations Crystal Formation Crystallization Cytosol Data Defect Dental Enamel Dental caries Enamel Formation Environment Epithelial Etiology Excision Extracellular Matrix Fracture Gelatin Goals Growth Health Human Human body Hydrolysis Hydroxyapatites In Situ In Vitro Inbred CFTR Mice Knockout Mice Knowledge Length Maintenance Maturation-Stage Ameloblast Minerals Modeling Molecular Morphology Mus Natural regeneration Oral health Peptide Hydrolases Periodicity Personal Satisfaction Predisposition Process Proteins Proton Pump Protons Research Resistance Risk Role Sodium Structure System Testing Thinness Time Tissues Tooth Fractures Tooth structure Wild Type Mouse amelogenin biomineralization calcium phosphate enamel matrix proteins extracellular improved in vitro testing in vivo mRNA Expression member mineralization mouse model novel novel strategies novel therapeutic intervention prevent protein expression receptor vacuolar H+-ATPase

项目摘要

PROJECT SUMMARY/ABSTRACT Mineralized enamel is the hardest tissue in the human body, and its proper formation is critical for the protection and maintenance of healthy teeth for a lifetime. Enamel biomineralization is directed by the epithelial derived ameloblasts. Ameloblasts secrete enamel matrix proteins, which are then hydrolyzed and replaced by hydroxyapatite crystals. Maturation stage ameloblasts modulate in waves to acidify approximately 80% of the mineralizing maturation stage matrix, with the remaining approximately 20% of the matrix remaining neutral. When pH cycling is disrupted, enamel formation is dysregulated, and the resulting enamel matrix is hypomineralized. Though an acidic environment is unfavorable to biomineralization, matrix acidification in enamel formation has been presumed to have a role in refinement of the hydroxyapatite (HAP) enamel crystals. However the mechanism(s) that control pH cycling remain unclear. In this project, we will use our novel polarized ameloblast culture system, along with Wdr72-/- and Cftr-/- mouse models, to test our central hypothesis that ameloblasts directly regulate pH cycling in the enamel matrix, to optimize enamel matrix mineralization. We will test this central hypothesis with the following specific aims. 1) To determine the role of ameloblasts in acidifying the enamel matrix; 2) To determine the effects of extracellular pH on calcium transport by ameloblasts; 3). To determine the role of matrix acidification on protein hydrolysis and HAP crystal formation. These studies will allow us to better understand the etiology of enamel hypomineralization, and will allow us to apply this knowledge to reduce the risk for of enamel defects. The long-term goal of our research is to determine how pH cycling by ameloblasts directs enamel matrix biomineralization to synthesize the unique prismatic mineralized structure that forms tooth enamel.

项目概要/摘要矿化牙釉质是人体最坚硬的组织，其正确形成对于保护牙釉质至关重要并终生维护健康的牙齿。牙釉质生物矿化是由上皮衍生的成釉细胞。成釉细胞分泌牙釉质基质蛋白，然后水解并被羟基磷灰石晶体。成熟阶段成釉细胞以波浪形式调节，酸化约 80% 的矿化成熟阶段基质，其余约 20% 的基质保持中性。当 pH 循环被破坏时，牙釉质的形成就会失调，产生的牙釉质基质就会被破坏。矿化不足。虽然酸性环境不利于生物矿化，但基质酸化据推测，牙釉质的形成在羟基磷灰石 (HAP) 牙釉质晶体的细化中发挥着重要作用。然而，控制 pH 循环的机制仍不清楚。在这个项目中，我们将使用我们新型的极化成釉细胞培养系统以及 Wdr72-/- 和 Cftr-/- 小鼠模型，以测试我们的中心假设，即成釉细胞直接调节牙釉质基质中的 pH 循环，优化牙釉质基质矿化。我们将通过以下具体目标来检验这一中心假设。 1) 至确定成釉细胞在酸化牙釉质基质中的作用； 2) 确定效果细胞外 pH 值对成釉细胞钙转运的影响； 3）。确定基质酸化对蛋白质水解和HAP晶体形成。这些研究将使我们更好地了解病因牙釉质矿化不足，并使我们能够应用这些知识来降低牙釉质缺陷的风险。我们研究的长期目标是确定成釉细胞的 pH 循环如何指导牙釉质基质生物矿化合成形成牙釉质的独特棱柱矿化结构。