Abstract
The role of dental pulp stem cells (DPSCs) in dental tissue regeneration is gaining attention because DPSCs can differentiate into odontoblasts and other specialized cell types. Epigenetic modification has been found to play an important role in cell differentiation and regulation, among which histone deacetylase (HDAC) is involved in suppressing genes by removing histone acetyl groups. The use of HDAC inhibitor to control this is increasing and has been widely studied by many researchers. This study aimed to induce differentiation by causing epigenetic changes in odontoblast-related genes and the MAPK signaling pathway in human dental pulp stem cells. Western blot and immunofluorescence staining showed increased expression of DMP-1, ALP, DSPP, and RUNX2 compared to the control. However, activation of the MAPK signaling system was similar to but slightly different from the expression of odontoblast-related proteins. After 3 days, as shown by MTT and LDH assays, proliferation decreased overall, but cytotoxicity decreased at only a specific concentration. We confirmed that there was no change in mRNA expression of caspase 3 or 9 using real-time PCR. In addition, flow cytometry analysis confirmed that differentiation occurred due to the decrease in the expression of the CD73 and CD146. Although overall proliferation was reduced due to the G2/M inhibition of the cell cycle, the expression of BCL-2 protected the cells from cell death. Overall, cell proliferation decreased in response to MS-275, but it did not induce cytotoxicity in 5 nM and 10 nM concentration and induces differentiation into odontoblast-like cells.
Highlights
Dental pulp stem cells (DPSCs) can be obtained from the third molars in a non-invasive way and differentiate into odontoblasts for dentin formation
Just as tideglusib, which is being developed as a treatment for Alzheimer’s syndrome, showed efficacy in tooth regeneration as a side effect [24], the results of the current study suggest that histone deacetylase (HDAC) inhibitors can be applied to stem cells as well as being used as anticancer drugs
Since HDAC classified as Zn2+-dependent (class I) is mainly located in the nucleus and ubiquitously rather than in specific tissues [6], there are reports that it has promoted the differentiation of osteogenesis and odontoblast in various cells such as adipose-derived stromal cells, bone marrow [29], umbilical cord [8], and dental pulp stem cells [30]
Summary
Dental pulp stem cells (DPSCs) can be obtained from the third molars in a non-invasive way and differentiate into odontoblasts for dentin formation. Epigenetics is the study of the genetic changes in gene expression that do not affect the DNA sequence, affecting how cells read genes. Mechanisms that have been identified so far include at least four systems: chromatin remodeling; DNA methylation; histone modification; and non-coding RNA expression. They are considered to initiate and maintain epigenetic changes. Among the epigenetic mechanisms mentioned, histone modification by histone acetyltransferases (HATs) and histone deacetylases (HDACs) is important role in regulating cell function [1,2,3]. HAT helps promote gene expression by moving acetyl groups to lysine residues in the histone tail, but HDAC suppresses gene expression by removing acetyl groups causing histone hypoacetylation [3,4]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
