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：
9890927
负责人：
Anne George
金额：
$ 37.98万
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/9890927
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 Structure 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/antagonist knock-down migration mouse model nerve supply novel preservation programs receptor regenerative repaired response rho scaffold 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.

项目概要深龋和牙髓暴露通常通过盖髓或部分牙髓治疗截肢以保留牙髓的活力，是防治龋齿的一大公益。牙髓干细胞（DPSC）的发现开辟了新的健康计划。牙髓-牙本质复合体再生或修复的途径使用成人干。组织再生和修复的细胞在再生医学中也很重要。组织工程的重要组成部分是生物活性信号分子。过去二十年我们一直在研究有机物的酸性磷蛋白骨和牙本质的基质除了在细胞外基质中的功能外，还有许多功能。这些蛋白质现在与刺激信号传导事件有关。直到最近，在牙本质基质中发现的功能是牙本质磷酸蛋白（DPP）。 DPP 被认为是结构性的；然而，最近的研究表明 DPP 我们的初步数据表明 DPP 可能在细胞信号传导中具有其他功能。激活Wnt信号通路促进牙齿成牙本质细胞分化 Wnt5a 是 DPSC 中 DPP 激活的特异性 Wnt。我们建议研究的 Wnt5a 信号下游效应是 β-catenin，我们发现 DPP 介导的这些效应器的激活。负责 DPSC 的分化及其迁移特性。假设我们建议使用分子方法：（a）研究分子 DPP 介导 Wnt 信号激活以稳定 β-catenin 的机制和 TAZ 导致 DPSC 分化为成牙本质细胞；(b) 检查 DPP 刺激对 RhoC GTPase 信号传导的影响及其对 DPSC 中肌动蛋白细胞骨架的重组导致细胞形状和 (c) 评估 DPP 作为牙本质异位模型中的治疗剂总的来说，这些研究的结果将揭示出前所未有的结果。由 DPP 调节的信号框架未来可用于开发治疗方法恢复丢失的受损或患病的牙本质牙髓复合体，并具有通向牙齿的活牙髓生存。