Calcium Regulation and Oral Health
钙调节和口腔健康
基本信息
- 批准号:8733843
- 负责人:
- 金额:$ 24.9万
- 依托单位:
- 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:
- 关键词:AdultAffectAmeloblastsAmelogenesisAmelogenesis ImperfectaAnimalsApplications GrantsBiological ProcessCalciumCellsCholecystokininCollaborationsCultured CellsDataDecision MakingDefectDentalDental EnamelDental cariesDentistsDevelopmentDiagnosisDissectionDyesEnamel OrganEpithelial CellsFamilyGenesGoalsImmune systemImmunofluorescence ImmunologicIn VitroIncisorIndiumIntakeKnockout MiceLinkMediatingMedicalMetabolismMichiganModelingMusMutateMutationOral healthParaffin EmbeddingPathway interactionsPatientsPhasePhenotypePrevention strategyProcessProtein IsoformsPublic HealthRattusRegulationRegulatory PathwayReportingReverse Transcriptase Polymerase Chain ReactionRoleRouteSTIM1 geneSignal TransductionStagingSubfamily lentivirinaeTestingThickTimeTissuesToxic effectUp-RegulationVisitWestern BlottingWidthWorkbiomineralizationcellular transductiondesignextracellulargenome-wide analysisinhibitor/antagonistmineralizationnovelpostnatalpreventuptake
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
项目总结/摘要
钙是一个广泛的生物功能的关键调节剂,也是组成中的关键元素
牙釉质在釉质形成的成熟阶段,随着釉质的发育,
晶体在宽度和厚度上膨胀。钙必须达到形成釉质层,但这个过程是如何
在成釉细胞中的调控机制知之甚少。目前釉质中Ca 2+转运的模型集中在
Ca 2+通过进入、转运和挤出步骤跨细胞通过。尽管有几个作品报道说
在运输和挤出步骤中,只有有限的信息可用于Ca 2+进入机制,
造釉细胞在这个资助计划中,我通过研究钙库运作的钙离子的作用来关注进入步骤。
释放激活的Ca 2+(CRAC)通道。CRAC通道包括重要的Ca 2+内流机制,
上皮细胞存在CRAC通道突变(STIM 1、ORAI 1)的患者,除了免疫缺陷外,
系统缺陷,伴有低钙化的釉质形成障碍。我的目标是确定Stim 1和Orai 1如何
参与Ca 2+进入以及如何调节这一过程。PI最近的工作表明,Stim 1,Orai 1
以及Ca 2+信号胆囊收缩素(Cck)和Cck抑制剂Rcan 1被鉴定为是
在成熟期显著上调。我已经通过qPCR、Western blot和IHC证实了这些结果。因此
Ca 2+通过CRAC通道流入成釉细胞以及该过程如何调节对于成釉细胞的增殖和分化是重要的。
发展健康的牙釉质。拟议的赠款申请提供的证据将有助于更好地
了解CRAC功能消除的全身效应。这也将有助于医生在
做出关于牙医访问具有CRAC通道突变的患者的决定,以防止
牙齿问题
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Rodrigo S. Lacruz其他文献
Casup2+/sup-activated chloride channel ANO1: A new regulator of osteoclast function
- DOI:
10.1016/j.ceca.2022.102633 - 发表时间:
2022-09-01 - 期刊:
- 影响因子:4.000
- 作者:
Nicola C. Partridge;Rodrigo S. Lacruz - 通讯作者:
Rodrigo S. Lacruz
The evolutionary history of the human face
人类面部的进化史
- DOI:
10.1038/s41559-019-0865-7 - 发表时间:
2019-04-15 - 期刊:
- 影响因子:14.500
- 作者:
Rodrigo S. Lacruz;Chris B. Stringer;William H. Kimbel;Bernard Wood;Katerina Harvati;Paul O’Higgins;Timothy G. Bromage;Juan-Luis Arsuaga - 通讯作者:
Juan-Luis Arsuaga
Rodrigo S. Lacruz的其他文献
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{{ truncateString('Rodrigo S. Lacruz', 18)}}的其他基金
Redox and Ca2+ signaling regulation of enamel mineralization
牙釉质矿化的氧化还原和 Ca2 信号传导调节
- 批准号:
10586833 - 财政年份:2023
- 资助金额:
$ 24.9万 - 项目类别:
Molecular mechanisms of oral deficiencies in Down syndrome
唐氏综合症口腔缺陷的分子机制
- 批准号:
10658410 - 财政年份:2023
- 资助金额:
$ 24.9万 - 项目类别:
Redox and Ca2+ signaling regulation of enamel mineralization
牙釉质矿化的氧化还原和 Ca2 信号传导调节
- 批准号:
10162310 - 财政年份:2018
- 资助金额:
$ 24.9万 - 项目类别:
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