Epigenetic regulation of osteogenic potential in mesenchymal stem cells derived from periodontal ligament

Abstract

Multipotent periodontal ligament stem cells (PDLSCs) have been recently shown to have both good osteogenic potential and proliferation capacity. Therefore, they are promising candidates not only for periodontal tissue repair but also for regenerative therapies in a broad range of bone diseases. However, they present different osteogenic potential. The molecular mechanism underlying osteogenic differentiation of PDLSCs is not well understood with very limited information available regarding their epigenetic background and regulation. Since cell fate is determined by lineage specific gene regulation and underlying epigenetic mechanisms such information is indispensable to safely apply PDLSCs in human clinical trials. The aim is to provide substantial amount of data that will help to fill in the gap in our understanding about osteogenesis and mesenchymal stem cell differentiation at the molecular level. Firstly, we will study genome wide global changes in DNA methylation/hydroxymethylation in cell populations with different osteogenic potential at 3rd and 10th day of osteogenesis. With this analysis, we aim to select potential epigenetic markers of preferential differentiation towards osteoblasts and evaluate if epigenetic profile is different between populations and how this profile change during osteogenic differentiation, reflecting at the gene expression. Secondly, we will investigate the possibility of RE1-transcription factor (REST) being a novel regulator of osteogenic differentiation, the action of which could be modified by a plant polyphenol resveratrol aiming to increase osteogenic differentiation in PDLSCs with low osteogenic potential and if it will be obtained by increase RUNX2 expression. Epigenetic regulation of genes involved in this mechanism and enzymes activity of epigenetic machinery will also be evaluated. (AU)