Departmental Papers (Dental)

Document Type

Journal Article

Date of this Version

7-2016

Publication Source

alcohol, dental pulp stem cells (DPSCs), epigenetics, DNA methylation, osteogenic differentiation, odontogenic differentiation, mineralization

Volume

17

Issue

1

Start Page

111

Last Page

121

DOI

10.1016/j.scr.2016.05.021

Abstract

Epigenetic changes, such as alteration of DNA methylation patterns, have been proposed as a molecular mechanism underlying the effect of alcohol on the maintenance of adult stem cells. We have performed genome-wide gene expression microarray and DNA methylome analysis to identify molecular alterations via DNA methylation changes associated with exposure of human dental pulp stem cells (DPSCs) to ethanol (EtOH). By combined analysis of the gene expression and DNA methylation, we have found a significant number of genes that are potentially regulated by EtOH-induced DNA methylation. As a focused approach, we have also performed a pathway-focused RT-PCR array analysis to examine potential molecular effects of EtOH on genes involved in epigenetic chromatin modification enzymes, fibroblastic markers, and stress and toxicity pathways in DPSCs. We have identified and verified that lysine specific demethylase 6B (KDM6B) was significantly dysregulated in DPSCs upon EtOH exposure. EtOH treatment during odontogenic/osteogenic differentiation of DPSCs suppressed the induction of KDM6B with alterations in the expression of differentiation markers. Knockdown of KDM6B resulted in a marked decrease in mineralization from implanted DPSCs in vivo. Furthermore, an ectopic expression of KDM6B in EtOH-treated DPSCs restored the expression of differentiation-related genes. Our study has demonstrated that EtOH-induced inhibition of KDM6B plays a role in the dysregulation of odontogenic/osteogenic differentiation in the DPSC model. This suggests a potential molecular mechanism for cellular insults of heavy alcohol consumption that can lead to decreased mineral deposition potentially associated with abnormalities in dental development and also osteopenia/osteoporosis, hallmark features of fetal alcohol spectrum disorders.

Copyright/Permission Statement

This is a post-peer-review, pre-copyedit version of an article published in Stem Cell Research. The final authenticated version is available online at: http://dx.doi.org/10.1016/j.scr.2016.05.021

Keywords

alcohol; dental pulp stem cells (DPSCs); epigenetics; DNA methylation; osteogenic differentiation; odontogenic differentiation; mineralization

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Date Posted: 01 March 2022

This document has been peer reviewed.