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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：
10453375
负责人：
Pamela K Den Besten
金额：
$ 9.05万
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：
2021
资助国家：
美国
起止时间：
2021-08-01 至 2022-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10453375
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. 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/文摘