CALCIUM REGULATION IN ORAL HEALTH

口腔健康中的钙调节

• 批准号: 8354594
• 负责人: Rodrigo S. Lacruz
• 金额: $ 10.69万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-13 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8354594
• 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; 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; 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

DESCRIPTION (provided by applicant): 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 PUBLIC HEALTH RELEVANCE: Calcium is critical for the normal biomineralization of enamel. Disruptions to calcium uptake by ameloblasts results in amelogenesis imperfecta. My goal is to analyze the function of calcium-store operated channels in enamel development.

描述（由申请人提供）：钙是广泛生物学功能的关键调节剂，也是牙齿搪瓷组成的关键要素。在ameleogeny的成熟阶段，随着搪瓷晶体的宽度和厚度扩展，Ca2+的需求会增加。钙必须达到形成的搪瓷层，但是如何在成成布中调节此过程的理解很少。 CA2+转运的当前模型通过条目，运输和挤出步骤集中于Ca2+的跨细胞通过。尽管已经报告了有关运输和挤出步骤的几项工作，但仅适用于CA2+进入机制到成核细胞中的有限信息。在此赠款建议中，我通过检查商店经营的CA2+释放激活CA2+（CRAC）渠道的作用来关注进入步骤。 CRAC通道包括上皮细胞中重要的CA2+涌入机制。除了免疫系统缺陷外，还存在与CRAC通道突变（STIM1，ORAI1）的突变患者，并具有降解的ameleogenesis 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+信号胆囊基蛋白（CCK）和CCK抑制剂RCAN1被确定为成熟的上调。我已经通过QPCR，Western印迹和IHC证实了这些结果。因此，Ca2+通过CRAC通道涌入成熟细胞以及如何调节该过程对于健康搪瓷的发展很重要。拟议的赠款申请贡献的证据将有助于更好地了解CRAC功能废除的系统性影响。这也将帮助医生做出有关牙医访问突变患者的决定，以防止牙齿问题 公共卫生相关性：钙对于搪瓷的正常生物矿化至关重要。成熟细胞对钙摄取的破坏会导致无肿瘤发生不完美。我的目标是分析钙商店操作的通道在搪瓷发育中的功能。