Growth factors-induced dentinogenesis

生长因子诱导的牙本质发生

基本信息

批准号：
10250621
负责人：
Emi Shimizu
金额：
$ 6.59万
依托单位：
RBHS-SCHOOL OF DENTAL MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-11-01 至 2022-08-31
项目状态：
已结题

项目摘要

Project summary: There is an increasing need to develop strategies for pulp regeneration therapy to overcome tooth injury due to caries, restorative procedures, or trauma. Currently, there is a significant gap in our understanding of the molecular and cellular mechanisms regulating reparative dentinogenesis. Our long-term goal is to gain fundamental knowledge on the human dental pulp cellular niche and to apply that knowledge to lessen the burdens of tooth injury due to caries, restorative procedures, or trauma. The objective for this application is to elucidate how the interactions between ephrinB1 and IGF-1 in the dental pulp niche induce dentinogenesis in vivo. The overarching hypothesis is that IGF-1 regulates cells of the tooth pulp niche, and induces dentinogenesis via ephrinB1. Guided by strong preliminary data, this hypothesis will be tested by pursuing the following two specific aims: Aim 1: Determine the mechanism by which ephrinB1 controls the number of odontoblast progenitors, their proliferation, and differentiation in the tooth pulp. And Aim 2: Determine the cellular and molecular mechanisms by which IGF-1 regulates ephrinB1 expression in vivo using mouse models and ex vivo using human DPSCs and human oral mucosa stem cells. An already-generated odontoblast-specific ephrinB1 knockout mouse lines (using cre driven by the DMP1 or osteocalcin promoters), and mouse lines of IGF-1 receptor (DMP1-IGF-1RKO) and the hepatic IGF-1 transgenic (HIT) line will be used to achieve the two aims. Importantly, initial characterization of our models indicates that both IGF-1 and ephrinB1 involved in dentinogenesis in vivo. The proposed research is conceptually innovative because we show, for the first time, the interactions between ephrinB1 and IGF-1 during dentinogenesis in vivo. Further, we offer a direct approach to determine these interactions using unique mouse models, as well as primary human dental pulp cell cultures. The proposed research is significant because it is expected to advance the field of regenerative endodontic procedures and will impact the overall effort to retain the natural tertiary dentin formation process following injury.

项目概要：越来越需要制定牙髓再生治疗策略来克服由于龋齿、修复手术或外伤导致的牙齿损伤。目前，有一个重大的我们对调节修复的分子和细胞机制的理解存在差距牙本质发生。我们的长期目标是获得有关人类牙髓的基础知识细胞生态位并应用这些知识来减轻龋齿造成的牙齿损伤的负担，恢复性手术或创伤。此应用程序的目的是阐明如何牙髓微环境中 ephrinB1 和 IGF-1 之间的相互作用诱导体内牙本质形成。总体假设是 IGF-1 调节牙髓微环境的细胞，并诱导通过 ephrinB1 进行牙本质发生。在强有力的初步数据的指导下，这一假设将得到检验通过追求以下两个具体目标：目标 1：确定机制 ephrinB1 控制成牙本质细胞祖细胞的数量、增殖和分化牙髓。目标 2：确定 IGF-1 发挥作用的细胞和分子机制使用小鼠模型体内调节 ephrinB1 表达，使用人 DPSC 体外调节 ephrinB1 表达和人类口腔粘膜干细胞。已生成的成牙本质细胞特异性 ephrinB1 敲除小鼠系（使用由 DMP1 或骨钙素启动子驱动的 cre）和小鼠 IGF-1 受体系 (DMP1-IGF-1RKO) 和肝 IGF-1 转基因 (HIT) 系将被用于实现两个目的。重要的是，我们模型的初步表征表明 IGF-1 和 ephrinB1 均参与体内牙本质形成。拟议的研究是概念上的创新，因为我们首次展示了 ephrinB1 之间的相互作用和 IGF-1 在体内牙本质形成过程中。此外，我们提供了一种直接方法来确定这些使用独特的小鼠模型以及原代人牙髓细胞培养物进行相互作用。这项研究意义重大，因为它有望推动再生领域的发展牙髓手术并将影响保留天然三级牙本质的整体努力损伤后的形成过程。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Epigenetic therapeutics in dental pulp treatment: Hopes, challenges and concerns for the development of next-generation biomaterials.

DOI：
10.1016/j.bioactmat.2023.04.013
发表时间：
2023-09
期刊：
BIOACTIVE MATERIALS
影响因子：
18.9
作者：
Duncan, Henry F.;Kobayashi, Yoshifumi;Kearney, Michaela;Shimizu, Emi
通讯作者：
Shimizu, Emi

iPSC-derived cranial neural crest-like cells can replicate dental pulp tissue with the aid of angiogenic hydrogel.

DOI：
10.1016/j.bioactmat.2021.11.014
发表时间：
2022-08
期刊：
Bioactive materials
影响因子：
18.9
作者：
Kobayashi Y;Nouet J;Baljinnyam E;Siddiqui Z;Fine DH;Fraidenraich D;Kumar VA;Shimizu E
通讯作者：
Shimizu E

The Critical Role of MMP13 in Regulating Tooth Development and Reactionary Dentinogenesis Repair Through the Wnt Signaling Pathway.