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Enamel biomineralization; the role of pH cycling

牙釉质生物矿化；

基本信息

批准号：
10577129
负责人：
Pamela K Den Besten
金额：
$ 6.46万
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 2024-02-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10577129
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.

项目总结/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齿至关重要。保持牙齿健康一辈子。牙釉质的生物矿化是由上皮衍生的造釉细胞成釉细胞分泌釉质基质蛋白，然后被水解并被替换为羟基磷灰石晶体。成熟期成釉细胞呈波浪状调节，使约80%的细胞酸化矿化成熟阶段基质，剩余约20%的基质保持中性。当pH循环被破坏时，釉质形成失调，并且所得的釉质基质被破坏。矿化不足虽然酸性环境不利于生物成矿，釉质形成被认为在羟基磷灰石（HAP）釉质晶体的细化中起作用。然而，控制pH循环的机制仍不清楚。在本项目中，我们将使用我们的新的极化成釉细胞培养系统，沿着Wdr 72-/-和Cftr-/-小鼠，模型，以检验我们的中心假设，即成釉细胞直接调节釉质基质中的pH循环，优化釉质基质矿化。我们将通过以下具体目标来检验这一中心假设。1)到确定成釉细胞在釉质基质酸化中的作用; 2）确定细胞外pH对成釉细胞钙转运的影响; 3）.为了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，并将使我们能够应用这些知识，以减少牙釉质缺陷的风险。本研究的长期目标是确定成釉细胞的pH循环如何指导釉质基质生物矿化合成独特的棱柱状矿化结构，形成牙釉质。