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
基本信息
- 批准号:10587230
- 负责人:
- 金额:$ 51.32万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-09-20 至 2027-06-30
- 项目状态:未结题
- 来源:
- 关键词:3-DimensionalATF6 geneAngiogenic FactorAngiogenic ProteinsAppearanceBindingBlood VesselsBone MatrixCalciumCell MaintenanceCell NucleusCell ProliferationCell Surface ReceptorsCell SurvivalCell physiologyCellsCellular AssayCellular StressCollagenCompetenceComplexComplex MixturesConfocal MicroscopyDataDental PulpDentinDiseaseEndoplasmic ReticulumEndothelial CellsEndotheliumEventExposure toExtracellular MatrixFGF2 geneFibronectinsGRP geneGRP78 geneGenetic MaterialsGenetic TranscriptionGenomicsGlucoseGoalsGrowthHarvestHistologyHormonesHydroxyapatitesImmuneImplantInflammatoryIntegral Membrane ProteinKnockout MiceMatrix MetalloproteinasesMediatingMetabolicMineralsModelingMusN-terminalNatural regenerationNuclearNutrientOutcomeOxygenP-CadherinPECAM1 geneParacrine CommunicationPhasePhenotypePlatelet-Derived Growth FactorProtein ArrayProteinsProteomicsRegenerative MedicineRegulationRoleSignal PathwaySignal TransductionSignaling MoleculeSliceTestingTherapeuticTherapeutic EffectThree-Dimensional ImagingTimeTissue EngineeringTissuesTooth structureTranscriptional ActivationTranscriptional RegulationTransforming Growth Factor betaTransgenic MiceVEGFA geneVWF geneValidationVascular Endothelial Growth FactorsVascular SystemVascularizationWaste ProductsWestern Blottingadult stem cellangiogenesisarmbonebone fracture repaircadherin 5dentin matrix protein 1endoplasmic reticulum stressengineered exosomesexosomeextracellulargenetic regulatory proteinhealingin vivoin vivo evaluationmigrationmineralizationmouse modelneovascularizationnoveloverexpressionparacrinepreconditioningprecursor cellprogenitorpromoterregeneration modelregenerativerepairedresponseresponse biomarkerscaffoldsensorstem cellssubcutaneoustherapy developmenttissue regenerationtissue repairtranscription factortranscriptome sequencingvasculogenesis
项目摘要
For dentin repair or regeneration, it is important to have the timely appearance of blood vessels.
Therefore, tissue-engineering strategies to regenerate the dentin-pulp complex require
establishment of vasculature to deliver oxygen, nutrients, hormones, immune cells, minerals
and also help in clearing cellular debris and metabolic waste products during the inflammatory
and regenerative phases of healing. DMP1 (dentin matrix protein1) is a key regulatory protein in
bone and dentin mineralization. We first demonstrated that it has a regulatory role in the
regulation of hydroxyapatite nucleation and growth in the extracellular matrices of bone and
dentin. Subsequently, we demonstrated that DMP1 was localized in the nucleus of
preosteoblasts and preodontoblasts and thus served as a signaling molecule and promoted the
differentiation of these precursor cells. Recently we discovered that DMP1 can stimulate the
release of intracellular calcium in preosteoblasts and preodontoblasts. Depletion of intracellular
calcium from the endoplasmic reticulum leads to ER stress. Cells cope with ER stress by
activating the “Unfolded protein response” (UPR). One of our recent observations is that DMP1
stimulation can promote the secretion of VEGF and other pro-angiogenic factors. Therefore, we
hypothesize that ER stress activated by DMP1 functions to promote the transformation of adult
stem cells such as dental pulp stem cells to endothelial cells and thereby promote
vasculogenesis. In order to determine the mechanism by which DMP1 promotes
vasculogenesis, we will examine the UPR signaling pathway. The UPR is initiated by three ER
transmembrane proteins, of which our preliminary data show that DMP1 stimulation activated
the ATF6 (Activating Transcription Factor 6) arm of the UPR. Accordingly, here we propose to
study the mechanism by which ATF6 mediate transcriptional regulation of VEGF under ER
stress. During dentin repair and regeneration, a major challenge is the maintenance of cell
viability which depends on the availability of a functional vascular system. Accordingly, we will
test the in-vivo vasculogenic competence and therapeutic potential of DMP1 in an in vivo pulp
regeneration model.
Understanding the complex functions of DMP1 could be valuable to develop therapies for
fracture repair in bone or in the tooth to restore lost, damaged or diseased dentin-pulp
complex.
为了修复或再生牙本质,及时出现血管是很重要的。
项目成果
期刊论文数量(0)
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科研奖励数量(0)
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专利数量(0)
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Anne George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:
$ 51.32万 - 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:
$ 51.32万 - 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:
$ 51.32万 - 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:
$ 51.32万 - 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:
$ 51.32万 - 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:
8465207 - 财政年份:2010
- 资助金额:
$ 51.32万 - 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:
$ 51.32万 - 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:
$ 51.32万 - 项目类别: