Mapping of DNA methylation-sensitive cellular processes in gingival and periodontal ligament fibroblasts in the context of periodontal tissue homeostasis.

Autor:	Lagosz-Cwik KB; Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland., Melnykova M; Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland., Nieboga E; Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland., Schuster A; Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland., Bysiek A; Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland., Dudek S; Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland., Lipska W; Department of Periodontology, Preventive Dentistry and Oral Medicine, Faculty of Medicine, Jagiellonian University Medical College, Kraków, Poland., Kantorowicz M; Department of Periodontology, Preventive Dentistry and Oral Medicine, Faculty of Medicine, Jagiellonian University Medical College, Kraków, Poland., Tyrakowski M; Chair of Oral Surgery, Faculty of Medicine, Jagiellonian University Medical College, Kraków, Poland., Darczuk D; Department of Periodontology, Preventive Dentistry and Oral Medicine, Faculty of Medicine, Jagiellonian University Medical College, Kraków, Poland., Kaczmarzyk T; Chair of Oral Surgery, Faculty of Medicine, Jagiellonian University Medical College, Kraków, Poland., Gilijamse M; Department of Oral and Maxillofacial Surgery and Oral Pathology, Amsterdam University Medical Center (Amsterdam UMC), Amsterdam, Netherlands.; Department of Oral and Maxillofacial Surgery, OLVG Hospital, Amsterdam, Netherlands., de Vries TJ; Department of Oral Cell Biology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and Vrije Universiteit Amsterdam, Amsterdam, Netherlands., Potempa J; Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland.; Department of Oral Immunology and Infectious Diseases, University of Louisville School of Dentistry, Louisville, KY, United States., Grabiec AM; Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2023 Jan 26; Vol. 14, pp. 1078031. Date of Electronic Publication: 2023 Jan 26 (Print Publication: 2023).
DOI:	10.3389/fimmu.2023.1078031
Abstrakt:	Interactions between gingival fibroblasts (GFs) and oral pathogens contribute to the chronicity of inflammation in periodontitis. Epigenetic changes in DNA methylation are involved in periodontitis pathogenesis, and recent studies indicate that DNA methyltransferase (DNMT) inhibitors may protect against epithelial barrier disruption and bone resorption. To assess the impact of DNMT inhibition on GFs, cells were cultured with decitabine (5-aza-2'-deoxycytidine, DAC) for 12 days to induce DNA hypomethylation. We observed several potentially detrimental effects of DAC on GF biological functions. First, extended treatment with DAC reduced GF proliferation and induced necrotic cell death. Second, DAC amplified Porphyromonas gingivalis - and cytokine-induced expression and secretion of the chemokine CCL20 and several matrix metalloproteinases (MMPs), including MMP1, MMP9, and MMP13. Similar pro-inflammatory effects of DAC were observed in periodontal ligament fibroblasts. Third, DAC upregulated intercellular adhesion molecule-1 (ICAM-1), which was associated with increased P. gingivalis adherence to GFs and may contribute to bacterial dissemination. Finally, analysis of DAC-induced genes identified by RNA sequencing revealed increased expression of CCL20 , CCL5 , CCL8 , CCL13 , TNF , IL1A , IL18, IL33 , and CSF3 , and showed that the most affected processes were related to immune and inflammatory responses. In contrast, the genes downregulated by DAC were associated with extracellular matrix and collagen fibril organization. Our observations demonstrate that studies of DNMT inhibitors provide important insights into the role of DNA methylation in cells involved in periodontitis pathogenesis. However, the therapeutic potential of hypomethylating agents in periodontal disease may be limited due to their cytotoxic effects on fibroblast populations and stimulation of pro-inflammatory pathways. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Lagosz-Cwik, Melnykova, Nieboga, Schuster, Bysiek, Dudek, Lipska, Kantorowicz, Tyrakowski, Darczuk, Kaczmarzyk, Gilijamse, de Vries, Potempa and Grabiec.)
Databáze:	MEDLINE
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