Calcium Regulation and Oral Health

钙调节和口腔健康

• 批准号: 8733843
• 负责人: Rodrigo S. Lacruz
• 金额: $ 24.9万
• 依托单位: NEW YORK UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-02-24 至 2017-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8733843
• 关键词: Adult; Affect; Ameloblasts; Amelogenesis; Amelogenesis Imperfecta; Animals; Applications Grants; Biological Process; Calcium; Cells; Cholecystokinin; Collaborations; Cultured Cells; Data; Decision Making; Defect; Dental; Dental Enamel; Dental caries; Dentists; Development; Diagnosis; Dissection; Dyes; Enamel Organ; Epithelial Cells; Family; Genes; Goals; Immune system; Immunofluorescence Immunologic; In Vitro; Incisor; Indium; Intake; Knockout Mice; Link; Mediating; Medical; Metabolism; Michigan; Modeling; Mus; Mutate; Mutation; Oral health; Paraffin Embedding; Pathway interactions; Patients; Phase; Phenotype; Prevention strategy; Process; Protein Isoforms; Public Health; Rattus; Regulation; Regulatory Pathway; Reporting; Reverse Transcriptase Polymerase Chain Reaction; Role; Route; STIM1 gene; Signal Transduction; Staging; Subfamily lentivirinae; Testing; Thick; Time; Tissues; Toxic effect; Up-Regulation; Visit; Western Blotting; Width; Work; biomineralization; cellular transduction; design; extracellular; genome-wide analysis; inhibitor/antagonist; mineralization; novel; postnatal; prevent; uptake

PROJECT SUMMARY/ABSTRACT Calcium is a key regulator of a broad range of biological functions and is also a key element in the composition of dental enamel. During the maturation stage of amelogenesis, Ca2+ requirements increase as enamel crystals expand in width and thickness. Calcium must reach the forming enamel layer but how this process is regulated in ameloblasts is poorly understood. The current model for Ca2+ transport in enamel focuses on the transcellular passage of Ca2+ via the entry, transit and extrusion steps. Whereas several works have reported on the transit and extrusion steps, only limited information is available for Ca2+ entry mechanisms into ameloblasts. In this grant proposal, I focus on the entry step by examining the role of the store-operated Ca2+ release-activated Ca2+ (CRAC) channels. CRAC channels comprise important Ca2+ influx mechanism in epithelial cells. Patients with mutations to CRAC channels (STIM1, ORAI1) present, in addition to immune system deficiencies, with hypocalcified amelogenesis imperfecta. My goal is to identify how Stim1 and Orai1 are involved in Ca2+ entry and how this process is regulated. Recent work by the PI indicates that Stim1, Orai1 as well as well as the Ca2+ signaling cholecystokinin (Cck) and the Cck inhibitor Rcan1 were identified as being significantly up-regulated in maturation. I have confirmed these results by qPCR, Western blot and IHC. Thus Ca2+ influx into ameloblasts via CRAC channels and how this process is regulated is important for the development of healthy enamel. Evidence contributed by the proposed grant application will help to better understand the systemic effects of CRAC function abrogation. This will also help medical practitioners in making decisions concerning dentist visits to patients with mutations to CRAC channels in order to prevent dental problems

项目总结/文摘