Intracellular and Extracellular function of dentin phosphophoryn
牙本质磷酸蛋白的细胞内和细胞外功能
基本信息
- 批准号:8465207
- 负责人:
- 金额:$ 37.3万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2010
- 资助国家:美国
- 起止时间:2010-07-01 至 2017-05-31
- 项目状态:已结题
- 来源:
- 关键词:ActinsAdhesionsAdhesivesAffinityAlveolarAmino AcidsAspartic AcidBindingBiological ProcessBone MatrixCalciumCalmodulinCell ProliferationCell SurvivalCell membraneCell physiologyCellsChargeCollagenCollagen FiberCollagen FibrilComplexCrystal FormationCytoskeletonDentinDentin FormationDentinogenesisDepositionDevelopmentEmbryoEventExhibitsExtracellular MatrixGelGene ExpressionGene ProteinsGene TargetingGenesGenetic TranscriptionGoalsGrowthGrowth and Development functionHumanHydroxyapatitesIn VitroInorganic ChemicalsIntegrin BindingIntegrinsIonsKidneyKnowledgeLeadLifeLigationLocationLungMechanicsMediatingMesenchymalMineralsMitogen-Activated Protein KinasesMolecularMorphologyMusMusculoskeletalNatural regenerationNeural CrestNeural Crest CellNuclear TranslocationOdontoblastsOrganismPhasePhosphoproteinsPhosphorylationPhosphotransferasesPhysiologic calcificationPlayPrecipitationProcessProductionPropertyProtein BiosynthesisProteinsRGD (sequence)ReportingRoleSecond Messenger SystemsSerineShapesSignal PathwaySignal TransductionSignaling MoleculeSiteStagingStem cellsStructureTemperatureTestingTimeTissuesTooth structureVertebratesbiomineralizationbonecalcium phosphatecalmodulin-dependent protein kinase IIcell typedemineralizationextracellularin vivoinsightinterestmacromoleculemineralizationphosphophorynpressurepublic health relevancereceptorresponsescaffoldsecond messenger
项目摘要
DESCRIPTION (provided by applicant): The proper mineralization of bones and teeth has great importance in normal human growth and development and musculoskeletal function. Disruption of normal biomineralization can lead to pathological mineralization or demineralization process. Understanding the complex process of biomineralization relies on knowledge of the structure and function of the organic matrix of mineralized tissues. Acidic phosphoproteins of the organic matrix of bone and dentin have been implicated as regulators of the nucleation process and growth of the inorganic calcium phosphate crystals of bone and teeth in vertebrates. The odontoblasts, which are dentin forming cells are neural crest derived and produce a unique set of phenotypic products. One such protein identified in the dentin matrix is dentin phosphophoryn (DPP). DPP isolated from dentin, has a unique composition with aspartyl and seryl residues comprising at least 75% of the amino acids with 85-90% of the serines being phosphorylated. Until recently, the function of DPP was thought to be structural; however, recent studies have suggested that DPP may have other functions in cell signaling. Therefore, the proposed studies are highly significant as it will provide important mechanistic insights into the function of DPP and its effects on cellular functions and in biological processes such as dentin biomineralization. We hypothesize that DPP is essential for the survival, terminal differentiation of the odontoblasts and in the mineralization of the organic matrix. To test this hypothesis we propose to use molecular approaches to: (a) investigate DPP-mediated adhesive signaling events leading to activation of cell proliferation and survival; (b) identify the mechanism by which DPP activates Smad1 and the downstream transcriptional responses leading to odontoblast terminal differentiation; (c) elucidate the role of DPP in mediating nucleation and growth of hydroxyapatite. Progress in understanding the function of DPP from the perspective of matrix mineralization and signaling has broad ramifications in the field of biomineralization.
描述(申请人提供):骨骼和牙齿的适当矿化对人类正常生长发育和肌肉骨骼功能具有重要意义。正常生物矿化的破坏可导致病理性矿化或脱矿过程。了解生物矿化的复杂过程依赖于矿化组织的有机基质的结构和功能的知识。骨和牙本质的有机基质的酸性磷蛋白已被认为是脊椎动物骨和牙齿的无机磷酸钙晶体的成核过程和生长的调节剂。成牙本质细胞是牙本质形成细胞,是神经嵴衍生的,产生一组独特的表型产物。在牙本质基质中鉴定的一种这样的蛋白质是牙本质磷酸蛋白(DPP)。从牙本质中分离的DPP具有独特的组成,其具有包含至少75%的氨基酸的丝氨酸残基和丝氨酸残基,其中85-90%的丝氨酸被磷酸化。直到最近,DPP的功能被认为是结构性的;然而,最近的研究表明,DPP可能在细胞信号传导中具有其他功能。因此,拟议的研究是非常重要的,因为它将提供重要的机制的见解DPP的功能及其对细胞功能和生物过程,如牙本质生物矿化的影响。我们推测DPP对于成牙本质细胞的存活、终末分化和有机基质的矿化是必不可少的。为了验证这一假设,我们建议使用分子方法:(a)调查DPP介导的粘附信号事件导致细胞增殖和存活的激活;(B)确定DPP激活Smad 1的机制和下游转录反应导致成牙本质细胞终末分化;(c)阐明DPP在介导羟基磷灰石成核和生长中的作用。从基质矿化和信号传导的角度理解DPP功能的进展在生物矿化领域具有广泛的分支。
项目成果
期刊论文数量(7)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Dentin phosphophoryn in the matrix activates AKT and mTOR signaling pathway to promote preodontoblast survival and differentiation.
基质中的牙本质磷酸化激活AKT和MTOR信号传导途径,以促进前牙本质细胞存活和分化。
- DOI:10.3389/fphys.2015.00221
- 发表时间:2015
- 期刊:
- 影响因子:4
- 作者:Eapen A;George A
- 通讯作者:George A
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Anne George其他文献
Anne George的其他文献
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{{ truncateString('Anne George', 18)}}的其他基金
Role of DMP1 Mediated Paracrine Signaling in Vasculogenesis
DMP1 介导的旁分泌信号在血管生成中的作用
- 批准号:
10707373 - 财政年份:2022
- 资助金额:
$ 37.3万 - 项目类别:
Role of DMP1 Mediated Paracrine Signaling in Vasculogenesis
DMP1 介导的旁分泌信号在血管生成中的作用
- 批准号:
10587230 - 财政年份:2022
- 资助金额:
$ 37.3万 - 项目类别:
The Role of DPP in Dental Pulp Stem Cells and its Potential in Tissue Regeneration
DPP 在牙髓干细胞中的作用及其在组织再生中的潜力
- 批准号:
10372969 - 财政年份:2019
- 资助金额:
$ 37.3万 - 项目类别:
The Role of DPP in Dental Pulp Stem Cells and its Potential in Tissue Regeneration
DPP 在牙髓干细胞中的作用及其在组织再生中的潜力
- 批准号:
9890927 - 财政年份:2019
- 资助金额:
$ 37.3万 - 项目类别:
The Role of DPP in Dental Pulp Stem Cells and its Potential in Tissue Regeneration
DPP 在牙髓干细胞中的作用及其在组织再生中的潜力
- 批准号:
10596123 - 财政年份:2019
- 资助金额:
$ 37.3万 - 项目类别:
The Role of DPP in Dental Pulp Stem Cells and its Potential in Tissue Regeneration
DPP 在牙髓干细胞中的作用及其在组织再生中的潜力
- 批准号:
10133458 - 财政年份:2019
- 资助金额:
$ 37.3万 - 项目类别:
Intracellular and Extracellular function of dentin phosphophoryn
牙本质磷酸蛋白的细胞内和细胞外功能
- 批准号:
8269568 - 财政年份:2010
- 资助金额:
$ 37.3万 - 项目类别:
Intracellular and Extracellular function of dentin phosphophoryn
牙本质磷酸蛋白的细胞内和细胞外功能
- 批准号:
8089541 - 财政年份:2010
- 资助金额:
$ 37.3万 - 项目类别:
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