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的正常生长发育和肌肉骨骼功能非常重要。破坏正常的生物矿化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对矿化组织有机基质的结构和功能的了解。骨和牙本质有机基质中的酸性磷蛋白被认为是脊椎动物骨和牙齿中无机钙磷酸盐晶体成核过程和生长的调节因子。成牙本质细胞是牙本质形成细胞,是神经脊来源的,能产生一套独特的表型产物。牙本质基质中发现的一种这样的蛋白质是牙本质磷蛋白(DPP)。DPP从牙本质中分离出来,具有独特的组成,天冬氨酸基和丝氨基残基至少占氨基酸的75%,85%-90%的丝氨酸被磷酸化。直到最近,DPP的功能还被认为是结构性的;然而,最近的研究表明,DPP可能在细胞信号转导中具有其他功能。因此,这项研究具有重要的意义,因为它将为DPP的功能及其对细胞功能和牙本质生物矿化等生物学过程的影响提供重要的机制见解。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。为了验证这一假说,我们建议使用分子方法:(A)研究DPP介导的黏附信号事件导致细胞增殖和存活的激活;(B)确定DPP激活Smad1及其下游转录反应导致成牙本质细胞终末分化的机制;(C)阐明DPP在调节羟基磷灰石成核和生长中的作用。从基质矿化和信号转导的角度理解DPP功能的进展在生物矿化领域具有广泛的意义。
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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