Abstract

The DNA demethylating agent, 5-Azacytidine (5Aza), and histone deacetylase inhibitor, valproic acid (Vpa), can improve the reprogramming efficiencies of pluripotent cells. This study aimed to examine the roles of 5Aza and Vpa in the dedifferentiation of epithelial cell rests of Malassez (ERM) into stem-like cells. Additionally, the ability of stem-like cells to differentiate into mesenchymal cells was evaluated. ERM was cultured in embryonic stem cell medium (ESCM) with 1 µM of 5Aza, or 2 mM of Vpa, or a combination of 5Aza and Vpa. The cells stimulated with both 5Aza and Vpa were named as progenitor-dedifferentiated into stem-like cells (Pro-DSLCs). The Pro-DSLCs cultured in ESCM alone for another week were named as DSLCs. The stem cell markers were significantly higher in the DSLCs than the controls (no additions). The mRNA and protein levels of the endothelial, mesenchymal stem, and osteogenic cell markers were significantly higher in the Pro-DSLCs and DSLCs than the controls. The combination of a demethylating agent and a deacetylated inhibitor induced the dedifferentiation of ERM into DSLCs. The Pro-DSLCs derived from ERM can be directly reprogrammed into mesenchymal-like cells without dedifferentiation into stem-like cells. Isolated ERM treated with epigenetic agents may be used for periodontal regeneration.

Details

Title
Direct reprogramming of epithelial cell rests of malassez into mesenchymal-like cells by epigenetic agents
Author
Yoshida Koki 1 ; Uehara Osamu 2 ; Kurashige Yoshihito 3 ; Paudel Durga 1 ; Onishi Aya 1 ; Neopane Puja 1 ; Hiraki Daichi 4 ; Morikawa Tetsuro 1 ; Harada Fumiya 5 ; Takai Rie 6 ; Sato, Jun 1 ; Saitoh Masato 3 ; Abiko Yoshihiro 1 

 Health Sciences University of Hokkaido, Division of Oral Medicine and Pathology, Department of Human Biology and Pathophysiology, School of Dentistry, Ishikari-Tobetsu, Japan (GRID:grid.412021.4) (ISNI:0000 0004 1769 5590) 
 Health Sciences University of Hokkaido, Division of Disease Control and Molecular Epidemiology, Department of Oral Growth and Development, School of Dentistry, Ishikari-Tobetsu, Japan (GRID:grid.412021.4) (ISNI:0000 0004 1769 5590) 
 Health Sciences University of Hokkaido, Division of Pediatric Dentistry, School of Dentistry, Ishikari-Tobetsu, Japan (GRID:grid.412021.4) (ISNI:0000 0004 1769 5590) 
 Health Sciences University of Hokkaido, Division of Reconstructive Surgery for Oral and Maxillofacial Region, Department of Human Biology and Pathophysiology, School of Dentistry, Ishikari-Tobetsu, Japan (GRID:grid.412021.4) (ISNI:0000 0004 1769 5590) 
 Health Sciences University of Hokkaido, Division of Oral and Maxillofacial Surgery, Department of Human Biology and Pathophysiology, School of Dentistry, Ishikari-Tobetsu, Japan (GRID:grid.412021.4) (ISNI:0000 0004 1769 5590) 
 Health Sciences University of Hokkaido, Research Institute of Health Sciences, Ishikari-Tobetsu, Japan (GRID:grid.412021.4) (ISNI:0000 0004 1769 5590) 
Publication year
2021
Publication date
2021
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2479190018
Copyright
© The Author(s) 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.