CALCIUM REGULATION IN ORAL HEALTH

口腔健康中的钙调节

• 批准号: 8510624
• 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 2014-02-23
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8510624
• 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

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

描述（由申请人提供）：钙是多种生物功能的关键调节剂，也是牙釉质组成的关键元素。在成釉发育成熟阶段，钙离子需求随着釉质晶体宽度和厚度的增加而增加。钙必须到达形成的牙釉质层，但这一过程如何在成釉细胞中被调节尚不清楚。目前的钙离子在牙釉质中的运输模型主要关注钙离子通过进入、运输和挤压步骤的跨细胞通道。虽然有一些研究报道了Ca2+进入成釉细胞的转运和挤压步骤，但只有有限的信息可用于Ca2+进入成釉细胞的机制。在本拨款提案中，我通过检查存储操作的Ca2+释放激活的Ca2+ (CRAC)通道的作用，专注于进入步骤。在上皮细胞中CRAC通道包含重要的Ca2+内流机制。CRAC通道（STIM1, ORAI1）突变的患者除了存在免疫系统缺陷外，还存在低钙化的淀粉性不完全性。我的目标是确定Stim1和Orai1是如何参与Ca2+进入的，以及这个过程是如何调节的。PI最近的研究表明，Stim1、Orai1以及Ca2+信号传导胆囊收缩素（Cck）和Cck抑制剂Rcan1在成熟过程中显著上调。我已经通过qPCR， Western blot和IHC证实了这些结果。因此，Ca2+通过CRAC通道流入成釉细胞以及如何调节这一过程对健康牙釉质的发育非常重要。拟议拨款申请提供的证据将有助于更好地理解CRAC功能废除的系统性影响。这也将有助于医生决定是否去看CRAC通道突变的患者，以预防牙齿问题

项目成果

Facial morphogenesis of the earliest europeans.

最早欧洲人的面部形态发生。

• DOI: 10.1371/journal.pone.0065199
• 发表时间: 2013
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Lacruz,RodrigoS;deCastro,JoséMaríaBermúdez;Martinón-Torres,María;O'Higgins,Paul;Paine,MichaelL;Carbonell,Eudald;Arsuaga,JuanLuis;Bromage,TimothyG
• 通讯作者: Bromage,TimothyG

Enamel: Molecular identity of its transepithelial ion transport system.

• DOI: 10.1016/j.ceca.2017.03.006
• 发表时间: 2017-07
• 期刊: Cell calcium
• 影响因子: 4
• 作者: Lacruz RS

Distinct growth of the nasomaxillary complex in Au. sediba.

金中鼻上颌复合体的明显生长。

• DOI: 10.1038/srep15175
• 发表时间: 2015
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Lacruz,RodrigoS;Bromage,TimothyG;O'Higgins,Paul;Toro-Ibacache,Viviana;Warshaw,Johanna;Berger,LeeR
• 通讯作者: Berger,LeeR