Epigenetic Regulation of Dental Pulp Stem Cell Fate

Abstract

Epigenetic regulation, mainly involving DNA methylation, histone modification, and noncoding RNAs, affects gene expression without modifying the primary DNA sequence and modulates cell fate. Mesenchymal stem cells derived from dental pulp, also called dental pulp stem cells (DPSCs), exhibit multipotent differentiation capacity and can promote various biological processes, including odontogenesis, osteogenesis, angiogenesis, myogenesis, and chondrogenesis. Over the past decades, increased attention has been attracted by the use of DPSCs in the field of regenerative medicine. According to a series of studies, epigenetic regulation is essential for DPSCs to differentiate into specialized cells. In this review, we summarize the mechanisms involved in the epigenetic regulation of the fate of DPSCs.

The Role of microRNAs in Pulp Inflammation

“…The function of miR-506 in pulp inflammation is not well-known, however, a study carried out by Wang et al coincides with that previously reported in the literature, since in this study, it was observed that in DPSCs stimulated with LPS, the expression of miR-506 was upregulated, activating the TLR-4 signaling pathway by upregulating sirtuin (SIRT)-1, together with an increase in the expression of pro-inflammatory proteins, such as IL-1β, IL-6, and TNF-α [93]. These findings suggest a pro-inflammatory role for miR-506 [94]; however, more studies are needed to understand the role of miR-506 in the pathogenesis of pulp disease.…”

“…Fyn is a member of the protein tyrosine kinase Src family, and its overexpression is associated with inflammation and odontogenesis [94]. These findings suggest that the induction of miR-125b overexpression in pulpal inflammation can reverse the inflammatory response and improve odontogenic differentiation, through the repression of Fyn [94,136].…”

“…Moreover, it has been observed that the overexpression of miR-Let-7c also represses the inflammatory response in DPSCs induced by LPS, through the inhibition of the NF-κB pathway mediated by DMP-1, promoting osteogenic differentiation through the inhibition of high mobility group AT-Hook (HMGA)-2/phosphoinositide-3-kinase (PI3K)/Akt signaling [129]. These findings show that miR-Let-7c may be a therapeutic potential during pulpal inflammation, since the induction of its overexpression leads to an anti-inflammatory effect, through blocking the NF-κB signaling pathway [94].…”

“…Regarding the expression of miR-584 during pulp inflammation, it has been reported that it was overexpressed in inflamed human pulps, compared to healthy pulps, having MAPK8 as a potential target gene, which is related to various biological processes, such as apoptosis, cell differentiation, and proliferation, as well as the TLR-4 signaling pathway [51,99]. Furthermore, a recent study reported that miR-584 expression was increased in aged dental pulp tissue compared to young dental pulp tissue [94,100]. These findings show that miR-584 has an important role in pulp tissue homeostasis; however, little information is available, and hence, it is necessary to carry out more studies, which help to better understand the role of miR-584 in pulp inflammation.…”

“…Regarding miR-125a, there is only one study in which it was observed that the stimulation of DPSCs with TNF-α induces the downregulation of the expression of miR-125b, while the expression of Fyn was upregulated [136]. Fyn is a member of the protein tyrosine kinase Src family, and its overexpression is associated with inflammation and odontogenesis [94]. These findings suggest that the induction of miR-125b overexpression in pulpal inflammation can reverse the inflammatory response and improve odontogenic differentiation, through the repression of Fyn [94,136].…”