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

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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.