Influence of oral non-metallic biomaterials on the cellular redox system and the odontogenic and angiogenic differentiation potential of dental pulp stem cells (DPSCs). Investigations about the key role of the Wnt-ß-catenin signal transduction

口腔非金属生物材料对细胞氧化还原系统以及牙髓干细胞（DPSC）成牙和血管生成分化潜力的影响。

• 批准号: 316032125
• 负责人: Professor Dr. Werner Geurtsen
• 金额: --
• 依托单位: Klinik für Zahnerhaltung, Parodontologie und Präventivzahnmedizin
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2016
• 资助国家: 德国
• 起止时间: 2015-12-31 至 2020-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/316032125?language=en
• 关键词: Influence; oral; non; metallic; biomaterials

The dental pulp is the target tissue of a substantial number of influences, mainly carious lesions and subsequent restorative procedures that may trigger regenerative pulp responses. The pulp response to dental restorative materials is a complicated process that is influenced by many factors, including the composition of the material, the nature and concentration of the eluted components or degradation products and the ability of the tissue to respond to these agents. The main effects of these materials on cells are oxidative stress, cell cycle delay and induction of apoptosis. Furthermore, our preliminary data showed that very low concentrations of resin monomers, which causing little or no cytotoxicity, are able to disturb the odontogenic differentiation processes of human oral mesenchymal stem cells (MSCs). Wnt signaling is an evolutionarily conserved mechanism that plays a critical role in mesenchymal tissue development and stem cell self-renewal. However no information exists about the regulation dental pulp stem cell by Wnt signaling as a response to pulp injuries. Results published by our group show, that TEGDMA, a dental co-monomer, activates the Wnt pathway. However, it is not clear to what extend this may affect the differentiation potential of hPSCs and if oxidative stress plays a crucial role.Therefore, aims of our research project to investigate and analyze the cellular and molecular mechanisms of pulp regenerative responses to dental resinous materials, focusing on the specific role of human pulp stem cells (hPSCs). We will investigate the effects of dental materials (HEMA, TEGDMA, BisGMA and eluates of composite resins) in modulating a physiological pulp regenerative response, expressed through the recruitment and odontogenic/ angiogenic differentiation of hPSCs. For the first time, we will also investigate the effects of these materials on Wnt pathway and the influence of Nrf2, a central redox sensitive transcription factor, on odontogenic/angiogenic differentiation processes and Wnt activation.

牙髓是许多影响的目标组织，主要是龋齿病变和随后可能引发牙髓再生反应的修复手术。牙髓对牙科修复材料的反应是一个复杂的过程，受到许多因素的影响，包括材料的成分、洗脱成分或降解产物的性质和浓度以及组织对这些试剂的反应能力。这些物质对细胞的主要作用是氧化应激、细胞周期延迟和诱导细胞凋亡。此外，我们的初步数据表明，极低浓度的树脂单体（几乎不产生细胞毒性）能够干扰人口腔间充质干细胞（MSC）的牙源性分化过程。 Wnt信号传导是一种进化上保守的机制，在间充质组织发育和干细胞自我更新中发挥着关键作用。然而，尚无关于通过 Wnt 信号调节牙髓干细胞作为对牙髓损伤的反应的信息。我们小组发表的结果表明，TEGDMA（一种牙科共聚单体）可激活 Wnt 通路。然而，目前尚不清楚这会在多大程度上影响 hPSC 的分化潜力，以及氧化应激是否起着至关重要的作用。因此，我们研究项目的目的是研究和分析牙髓对牙科树脂材料再生反应的细胞和分子机制，重点关注人牙髓干细胞（hPSC）的具体作用。我们将研究牙科材料（HEMA、TEGDMA、BisGMA 和复合树脂洗脱液）在调节生理牙髓再生反应中的作用，该反应通过 hPSC 的募集和牙源/血管生成分化来表达。我们还将首次研究这些材料对 Wnt 通路的影响，以及中央氧化还原敏感转录因子 Nrf2 对牙源/血管生成分化过程和 Wnt 激活的影响。