title: Epigenetic modulation of dental pulp stem cells: implications for regenerative endodontics.
abstract: Dental pulp stem cells (DPSCs) offer significant potential for use in regenerative endodontics, and therefore, identifying cellular regulators that control stem cell fate is critical to devising novel treatment strategies. Stem cell lineage commitment and differentiation are regulated by an intricate range of host and environmental factors of which epigenetic influence is considered vital. Epigenetic modification of DNA and DNA-associated histone proteins has been demonstrated to control cell phenotype and regulate the renewal and pluripotency of stem cell populations. The activities of the nuclear enzymes, histone deacetylases, are increasingly being recognized as potential targets for pharmacologically inducing stem cell differentiation and dedifferentiation. Depending on cell maturity and niche in vitro, low concentration histone deacetylase inhibitor (HDACi) application can promote dedifferentiation of several post-natal and mouse embryonic stem cell populations and conversely increase differentiation and accelerate mineralization in DPSC populations, whilst animal studies have shown an HDACi-induced increase in stem cell marker expression during organ regeneration. Notably, both HDAC and DNA methyltransferase inhibitors have also been demonstrated to dramatically increase the reprogramming of somatic cells to induced pluripotent stem cells (iPSCs) for use in regenerative therapeutic procedures. As the regulation of cell fate will likely remain the subject of intense future research activity, this review aims to describe the current knowledge relating to stem cell epigenetic modification, focusing on the role of HDACi on alteration of DPSC phenotype, whilst presenting the potential for therapeutic application as part of regenerative endodontic regimens.
authors.affiliation: Division of Restorative Dentistry & Periodontology, Dublin Dental University Hospital, Trinity College, Dublin, Ireland.
authors.forename: H F
authors.initials: HF
authors.lastname: Duncan
authors.affiliation: Oral Biology, School of Dentistry, University of Birmingham, Birmingham, UK.
authors.forename: A J
authors.initials: AJ
authors.lastname: Smith
authors.affiliation: Material Science Unit, Dublin Dental University Hospital, Trinity College, Dublin, Ireland.
authors.forename: G J P
authors.initials: GJ
authors.lastname: Fleming
authors.affiliation: Oral Biology, School of Dentistry, University of Birmingham, Birmingham, UK.
authors.forename: P R
authors.initials: PR
authors.lastname: Cooper
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D003782:Dental Pulp / Q000166:cytology*; D004708:Endodontics; D057890:Epigenomics; D051379:Mice; D012038:Regeneration; D013234:Stem Cells
keywords: dental pulp stem cell; differentiation; epigenetics; histone deacetylase inhibitors; regenerative endodontics