Calcium Regulation and Oral Health

钙调节和口腔健康

基本信息

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
项目类别：
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

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

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项目摘要

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

项目摘要/摘要钙是广泛生物学功能的关键调节剂，也是组成的关键要素牙釉质。在提高发生的成熟阶段，Ca2+需求随着搪瓷的增加而增加晶体的宽度和厚度膨胀。钙必须达到形成的搪瓷层，但是这个过程是如何在青木细胞中调节的知识很少。搪瓷中Ca2+传输的当前模型的重点是 Ca2+的跨细胞通过通过条目，运输和挤出步骤。虽然有几项著作报告在运输和挤出步骤上，仅适用于CA2+进入机构的有限信息成熟的细胞。在此赠款建议中，我通过检查商店经营的CA2+的作用来关注进入步骤释放激活的Ca2+（CRAC）通道。 CRAC通道包括重要的CA2+涌入机制上皮细胞。除了免疫外，还存在于CRAC通道突变的患者（STIM1，ORAI1）系统缺陷，具有降解的ameleogeny imperfecta。我的目标是确定STIM1和ORAI1如何参与CA2+进入以及如何调节此过程。 PI的最新工作表明Stim1，Orai1 以及Ca2+信号传导胆囊化素（CCK）和CCK抑制剂RCAN1均被确定为在成熟中显着上调。我已经通过QPCR，Western印迹和IHC证实了这些结果。因此 Ca2+通过CRAC通道流入成成成成本，以及如何调节此过程对发展健康的搪瓷。拟议的赠款申请提供的证据将有助于改善了解CRAC功能废除的系统效应。这也将帮助医生关于牙医访问突变的患者对CRAC通道的决定，以防止牙科问题