Epigenetic Modifications of Histones in Periodontal Disease.
Periodontitis is a chronic infectious disease driven by dysbiosis, an imbalance between commensal bacteria and the host organism. Periodontitis is a leading cause of tooth loss in adults and occurs in about 50% of the US population. In addition to the clinical challenges associated with treating periodontitis, the progression and chronic nature of this disease seriously affect human health. Emerging evidence suggests that periodontitis is associated with mechanisms beyond bacteria-induced protein and tissue degradation. Here, we hypothesize that bacteria are able to induce epigenetic modifications in oral epithelial cells mediated by histone modifications. In this study, we found that dysbiosis in vivo led to epigenetic modifications, including acetylation of histones and downregulation of DNA methyltransferase 1. In addition, in vitro exposure of oral epithelial cells to lipopolysaccharides resulted in histone modifications, activation of transcriptional coactivators, such as p300/CBP, and accumulation of nuclear factor-κB (NF-κB). Given that oral epithelial cells are the first line of defense for the periodontium against bacteria, we also evaluated whether activation of pathogen recognition receptors induced histone modifications. We found that activation of the Toll-like receptors 1, 2, and 4 and the nucleotide-binding oligomerization domain protein 1 induced histone acetylation in oral epithelial cells. Our findings corroborate the emerging concept that epigenetic modifications play a role in the development of periodontitis.
Laboratory of Epithelial Biology, University of Michigan School of Dentistry, Ann Arbor, MI, USA Department of Oral Pathology, School of Dentistry, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI, USA.
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Martins
Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI, USA Department of Pathology and Comprehensive Cancer Center, The University of Michigan Medical School, Ann Arbor, MI, USA.
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Jiao
Department of Periodontology, Institute of Odontology, University of Gothenburg, Sweden.
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Larsson
Laboratory of Epithelial Biology, University of Michigan School of Dentistry, Ann Arbor, MI, USA Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI, USA.
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Almeida
Laboratory of Epithelial Biology, University of Michigan School of Dentistry, Ann Arbor, MI, USA Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI, USA.
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Garaicoa-Pazmino
Laboratory of Epithelial Biology, University of Michigan School of Dentistry, Ann Arbor, MI, USA Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI, USA.
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Le
Laboratory of Epithelial Biology, University of Michigan School of Dentistry, Ann Arbor, MI, USA Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI, USA.
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Squarize
Department of Pathology and Comprehensive Cancer Center, The University of Michigan Medical School, Ann Arbor, MI, USA.
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Inohara
Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI, USA.
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Giannobile
Laboratory of Epithelial Biology, University of Michigan School of Dentistry, Ann Arbor, MI, USA Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI, USA rcastilh@umich.edu.
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Castilho
D000107:Acetylation; D016301:Alveolar Bone Loss / Q000382:microbiology; D000818:Animals; D002460:Cell Line; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000032:analysis; D004195:Disease Models, Animal; D064806:Dysbiosis / Q000235:genetics; D044127:Epigenesis, Genetic / Q000235:genetics*; D004847:Epithelial Cells / Q000378:metabolism / Q000382:microbiology; D016967:Fusobacterium nucleatum / Q000235:genetics / Q000502:physiology; D005889:Gingival Recession / Q000382:microbiology; D006657:Histones / Q000235:genetics*; D054884:Host-Pathogen Interactions / Q000235:genetics; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism / Q000382:microbiology; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D009061:Mouth Mucosa / Q000166:cytology / Q000382:microbiology; D016328:NF-kappa B / Q000032:analysis; D053474:Nod1 Signaling Adaptor Protein / Q000032:analysis; D017622:Periodontal Attachment Loss / Q000382:microbiology; D010518:Periodontitis / Q000235:genetics* / Q000382:microbiology; D046188:Protein Modification, Translational / Q000235:genetics; D051194:Toll-Like Receptor 1 / Q000032:analysis; D051195:Toll-Like Receptor 2 / Q000032:analysis; D051197:Toll-Like Receptor 4 / Q000032:analysis; D050880:p300-CBP Transcription Factors / Q000032:analysis
D006657:Histones; D008070:Lipopolysaccharides; D016328:NF-kappa B; D053474:Nod1 Signaling Adaptor Protein; D051194:Toll-Like Receptor 1; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; D050880:p300-CBP Transcription Factors
NOD1; TLRs; bacteria; histone acetylation; lipopolysaccharides; oral mucosa