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

基本信息

批准号：
10372969
负责人：
Anne George
金额：
$ 37.6万
依托单位：
UNIVERSITY OF ILLINOIS AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-04-01 至 2024-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10372969
关键词：
Actins Amputation Biological Assay Bone Matrix Calcium Cell Shape Cells Chemicals Clinical Complex Cues Cytoskeleton DSPP gene Data Dental Dental Pulp Dental Pulp Capping Dental caries Dentin Deposition Disease Event Extracellular Matrix Extracellular Matrix Proteins F-Actin Future Gene Expression Genetic Transcription Guanosine Triphosphate Phosphohydrolases Histology Immobilization Immunofluorescence Immunologic Immunoprecipitation In Vitro Injury Ligands MAPT gene Mechanics Mediating Methods Microtubules Modeling Molecular Natural regeneration Odontoblasts Phosphoproteins Property Proteins Public Health Regenerative Medicine Reverse Transcriptase Polymerase Chain Reaction Role Signal Transduction Signaling Molecule Site Small Interfering RNA Specificity Stains Stimulus Stress Fibers Testing Therapeutic Agents Time Tissue Engineering Tissues Tooth root structure Tooth structure Trauma Tubular formation Vascularization WNT Signaling Pathway Western Blotting adult stem cell base beta catenin cell motility cytokine cytotoxicity experimental study in vivo Model inhibitor knock-down migration mouse model nerve supply novel preservation programs receptor regeneration potential repaired response rho scaffold stem cell migration stem cell population stem cells therapy development tissue regeneration tissue repair tissue stem cells transplant model wound healing

项目摘要

PROJECT SUMMARY Deep caries and pulp exposures are normally treated by pulp capping or partial pulp amputation to preserve the vitality of the pulp. Control of dental caries is a major public health program. Discovery of the dental pulp stem cells (DPSCs) have opened up new avenues for regeneration or repair of the pulp-dentin complex. The use of adult stem cells for tissue regeneration and repair is important in regenerative medicine. Another important component for tissue engineering is a bioactive signaling molecule. For the last two decades we have been studying the acidic phosphoproteins of the organic matrix of bone and dentin. Besides their function in the extracellular matrix, many of these proteins are now implicated in stimulating signaling events. One such protein identified in the dentin matrix is dentin phosphophoryn (DPP). 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. Our preliminary data indicate that DPP activates the Wnt signaling pathway to promote odontoblast differentiation of the dental pulp stem cells. Wnt5a was the specific Wnt activated by DPP in DPSCs. The downstream effectors of Wnt5a signaling that we propose to investigate are β-catenin, TAZ and RhoC. We hypothesize that these DPP-mediated activation of these effectors are responsible for differentiation of DPSC's and their migratory properties. To test this hypothesis we propose to use molecular approaches : (a) To investigate the molecular mechanisms by which DPP mediates the activation of Wnt signaling to stabilize β-catenin and TAZ resulting in the differentiation of DPSCs into odontoblasts; (b) To examine the influence of DPP stimulation on RhoC GTPase signaling and its effect on the reorganization of the actin cytoskeleton in DPSCs leading to changes in cell shape and migration; (c ) To evaluate DPP as a therapeutic agent in an ectopic model for dentin- pulp regeneration. Overall, results from these studies would reveal an unprecedented signaling framework modulated by DPP that could be utilized in the future to develop therapies to restore lost damaged or diseased dentin-pulp complex with a vital pulp leading to tooth survival.

项目摘要龋齿和果肉暴露通常通过纸浆帽或部分果肉处理截肢以保留牙髓的活力。健康计划。用于牙髓蛋白复合物的再生或修复的途径。用于再生医学的组织再生细胞。组织工程的重要组成部分是生物活性信号分子。最近二十年，我们一直在研究有机的酸性磷蛋白骨骼和牙本质的矩阵除了它们在外部矩阵中的功能外这些蛋白质现在与刺激性蛋白质有关在牙本质基质中鉴定出的是牙本质磷酸化（DPP）。 DPP是结构性的，但是最近的研究表明DPP 在细胞信号中可能具有其他功能。激活Wnt信号传导途径以促进牙齿的Odontoblast差异化。纸浆干细胞我们建议研究的Wnt5a信号的下游效应子是β-catenin，是β-catenin， TAZ和RHOC，我们假设DPP介导的激活负责DPSC和迁移属性的分化假设我们建议使用分子方法：（a）研究分子 DPP介导Wnt信号传导激活以稳定β-cateninin的机制和TAZ导致DPSC将DPSC分化为odontoblasts； DPP刺激对RHOC GTPase信号传导的影响，是ETS对 DPSC中肌动蛋白细胞骨架的重组，导致细胞形状变化Ande 迁移;（C）在异位模型中评估DPP作为治疗剂纸浆再生。由DPP模块化的信号传导框架将来可以开发疗法恢复损失的损坏或患病的Dentin-Pulp Comp Complex，并带有VITALP导致Toto 生存。