Epigenetic adaptations of the masticatory mucosa to periodontal inflammation

Clinical Epigenetics

Christian Graetz¹  Corinna Bruckmann²  Ingmar Staufenbiel³  Carsten Rendenbach⁴  Henrik Dommisch⁵  Gesa M. Richter⁵  Arne S. Schaefer⁵  Yvonne Jockel-Schneider⁶  Søren Jepsen⁷  Gunar Wagner⁸  Andre Franke⁹  Jochen Kruppa^1,10  Orlando Martins^1,11  H. Gencay Keceli^1,12  Rahime M. Nohutcu^1,12  Emel Tuğba Ataman-Duruel^1,12  Nicole Pischon^1,13 

[1]Clinic of Conservative Dentistry and Periodontology, University Medical Center Schleswig-Holstein, Arnold-Heller-Straße 3, 24105, Kiel, Germany

[2]Department of Conservative Dentistry and Periodontology, Medical University Vienna, School of Dentistry, Sensengasse 2a, 1090, Vienna, Austria

[3]Department of Conservative Dentistry, Periodontology & Preventive Dentistry, School of Dentistry, Hannover Medical School (MHH), Carl-Neuberg-Str. 1, 30625, Hannover, Germany

[4]Department of Oral and Maxillofacial Surgery, Charité - Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität Zu Berlin, and Berlin Institute of Health, Augustenburger Platz 1, 13353, Berlin, Germany

[5]Department of Periodontology and Synoptic Dentistry, Oral Medicine and Oral Surgery, Institute for Dental and Craniofacial Sciences, Charité – Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität Zu Berlin, and Berlin Institute of Health, Aßmannshauser Str. 4-6, 14197, Berlin, Germany

[6]Department of Periodontology, Clinic of Preventive Dentistry and Periodontology, University Medical Center of the Julius-Maximilians-University, Pleicherwall, 97070, Würzburg, Germany

[7]Department of Periodontology, Operative and Preventive Dentistry, University of Bonn, Welschnonnenstraße 17, 53111, Bonn, Germany

[8]Department of Restorative Dentistry and Periodontology, University Medical Center Leipzig, 04103, Leipzig, Germany

[9]Institute of Clinical Molecular Biology, Christian-Albrechts-University, Rosalind-Franklin-Straße 12, 24105, Kiel, Germany

[10]Institute of Medical Informatics, Charité – Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität Zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117, Berlin, Germany

[11]Institute of Periodontology, Institute of Medicine and Oral Surgery, Dentistry Department, Faculty of Medicine, University of Coimbra, Av. Bissaya Barreto, Bloco de Celas, 3000-075, Coimbra, Portugal

[12]Periodontology Department, Faculty of Dentistry, Hacettepe University, 06230, Sihhiye/Altindag/Ankara, Turkey

[13]Private Practice, Karl-Marx-Straße 24, 12529, Schönefeld, Germany

关键词: EWAS;    Methylation;    Periodontitis;    Gingiva;    Inflammation;    Cell type deconvolution;    ROBO2;    PTP4A3;   

DOI  :  10.1186/s13148-021-01190-7

来源: Springer

【 摘 要 】

BackgroundIn mucosal barrier interfaces, flexible responses of gene expression to long-term environmental changes allow adaptation and fine-tuning for the balance of host defense and uncontrolled not-resolving inflammation. Epigenetic modifications of the chromatin confer plasticity to the genetic information and give insight into how tissues use the genetic information to adapt to environmental factors. The oral mucosa is particularly exposed to environmental stressors such as a variable microbiota. Likewise, persistent oral inflammation is the most important intrinsic risk factor for the oral inflammatory disease periodontitis and has strong potential to alter DNA-methylation patterns. The aim of the current study was to identify epigenetic changes of the oral masticatory mucosa in response to long-term inflammation that resulted in periodontitis.Methods and resultsGenome-wide CpG methylation of both inflamed and clinically uninflamed solid gingival tissue biopsies of 60 periodontitis cases was analyzed using the Infinium MethylationEPIC BeadChip. We validated and performed cell-type deconvolution for infiltrated immune cells using the EpiDish algorithm. Effect sizes of DMPs in gingival epithelial and fibroblast cells were estimated and adjusted for confounding factors using our recently developed “intercept-method”. In the current EWAS, we identified various genes that showed significantly different methylation between periodontitis-inflamed and uninflamed oral mucosa in periodontitis patients. The strongest differences were observed for genes with roles in wound healing (ROBO2, PTP4A3), cell adhesion (LPXN) and innate immune response (CCL26, DNAJC1, BPI). Enrichment analyses implied a role of epigenetic changes for vesicle trafficking gene sets.ConclusionsOur results imply specific adaptations of the oral mucosa to a persistent inflammatory environment that involve wound repair, barrier integrity, and innate immune defense.

【 授权许可】

CC BY