Loricrin and Cytokeratin Disorganisation in Severe Forms of Periodontitis

Objective: The aim of this research was to investigate the role of the cornified epithelium, the outermost layer of the oral mucosa, engineered to prevent water loss and microorganism invasion, in severe forms of periodontitis (stage III or IV, grade C). Methods: Porphyromonas gingivalis, a major pe...

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Main Authors: Raisa Queiroz Catunda, Karen Ka-yan Ho, Srushti Patel, Christopher Bryant Roy, Maria Alexiou, Liran Levin, Benjamin J. Ulrich, Mark H. Kaplan, Maria Febbraio
Format: Article
Language:English
Published: Elsevier 2023-12-01
Series:International Dental Journal
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S0020653923000898
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author Raisa Queiroz Catunda
Karen Ka-yan Ho
Srushti Patel
Christopher Bryant Roy
Maria Alexiou
Liran Levin
Benjamin J. Ulrich
Mark H. Kaplan
Maria Febbraio
author_facet Raisa Queiroz Catunda
Karen Ka-yan Ho
Srushti Patel
Christopher Bryant Roy
Maria Alexiou
Liran Levin
Benjamin J. Ulrich
Mark H. Kaplan
Maria Febbraio
author_sort Raisa Queiroz Catunda
collection DOAJ
description Objective: The aim of this research was to investigate the role of the cornified epithelium, the outermost layer of the oral mucosa, engineered to prevent water loss and microorganism invasion, in severe forms of periodontitis (stage III or IV, grade C). Methods: Porphyromonas gingivalis, a major periodontal disease pathogen, can affect cornified epithelial protein expression through chronic activation of signal transducer and activator of transcription 6 (Stat6). We used a mouse model, Stat6VT, that mimics this to determine the effects of barrier defect on P gingivalis–induced inflammation, bone loss, and cornified epithelial protein expression, and compared histologic and immunohistologic findings with tissues obtained from human controls and patients with stage III and IV, grade C disease. Alveolar bone loss in mice was assessed using micro-computerised tomography, and soft tissue morphology was qualitatively and semi-quantitatively assessed by histologic examination for several proteins, including loricrin, filaggrin, cytokeratin 1, cytokeratin 14, a proliferation marker, a pan-leukocyte marker, as well as morphologic signs of inflammation. Relative cytokine levels were measured in mouse plasma by cytokine array. Results: In the tissues from patients with periodontal disease, there were greater signs of inflammation (rete pegs, clear cells, inflammatory infiltrates) and a decrease and broadening of expression of loricrin and cytokeratin 1. Cytokeratin 14 expression was also broader and decreased in stage IV. P gingivalis–infected Stat6VT mice showed greater alveolar bone loss in 9 out of 16 examined sites, and similar patterns of disruption to human patients in expression of loricrin and cytokeratins 1 and 14. There were also increased numbers of leukocytes, decreased proliferation, and greater signs of inflammation compared with P gingivalis–infected control mice. Conclusions: Our study provides evidence that changes in epithelial organisation can exacerbate the effects of P gingivalis infection, with similarities to the most severe forms of human periodontitis.
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spelling doaj.art-d7e2955a9c9f48c0b8f05e1695ff1dad2023-11-01T04:45:45ZengElsevierInternational Dental Journal0020-65392023-12-01736862872Loricrin and Cytokeratin Disorganisation in Severe Forms of PeriodontitisRaisa Queiroz Catunda0Karen Ka-yan Ho1Srushti Patel2Christopher Bryant Roy3Maria Alexiou4Liran Levin5Benjamin J. Ulrich6Mark H. Kaplan7Maria Febbraio8Department of Dentistry, College of Health Sciences, University of Alberta, Edmonton, Alberta, CanadaDepartment of Dentistry, College of Health Sciences, University of Alberta, Edmonton, Alberta, CanadaDepartment of Dentistry, College of Health Sciences, University of Alberta, Edmonton, Alberta, CanadaDepartment of Dentistry, College of Health Sciences, University of Alberta, Edmonton, Alberta, CanadaDepartment of Dentistry, College of Health Sciences, University of Alberta, Edmonton, Alberta, CanadaDepartment of Dentistry, College of Health Sciences, University of Alberta, Edmonton, Alberta, CanadaNorthwestern University, Chicago, Illinois, USADepartment of Microbiology & Immunology, School of Medicine, Indiana University, Indianapolis, Indiana, USADepartment of Dentistry, College of Health Sciences, University of Alberta, Edmonton, Alberta, Canada; Corresponding author. Department of Dentistry, College of Health Sciences, University of Alberta, 7020M, Katz, 11361-87th Avenue, Edmonton, Alberta, Canada, T6G 2E1.Objective: The aim of this research was to investigate the role of the cornified epithelium, the outermost layer of the oral mucosa, engineered to prevent water loss and microorganism invasion, in severe forms of periodontitis (stage III or IV, grade C). Methods: Porphyromonas gingivalis, a major periodontal disease pathogen, can affect cornified epithelial protein expression through chronic activation of signal transducer and activator of transcription 6 (Stat6). We used a mouse model, Stat6VT, that mimics this to determine the effects of barrier defect on P gingivalis–induced inflammation, bone loss, and cornified epithelial protein expression, and compared histologic and immunohistologic findings with tissues obtained from human controls and patients with stage III and IV, grade C disease. Alveolar bone loss in mice was assessed using micro-computerised tomography, and soft tissue morphology was qualitatively and semi-quantitatively assessed by histologic examination for several proteins, including loricrin, filaggrin, cytokeratin 1, cytokeratin 14, a proliferation marker, a pan-leukocyte marker, as well as morphologic signs of inflammation. Relative cytokine levels were measured in mouse plasma by cytokine array. Results: In the tissues from patients with periodontal disease, there were greater signs of inflammation (rete pegs, clear cells, inflammatory infiltrates) and a decrease and broadening of expression of loricrin and cytokeratin 1. Cytokeratin 14 expression was also broader and decreased in stage IV. P gingivalis–infected Stat6VT mice showed greater alveolar bone loss in 9 out of 16 examined sites, and similar patterns of disruption to human patients in expression of loricrin and cytokeratins 1 and 14. There were also increased numbers of leukocytes, decreased proliferation, and greater signs of inflammation compared with P gingivalis–infected control mice. Conclusions: Our study provides evidence that changes in epithelial organisation can exacerbate the effects of P gingivalis infection, with similarities to the most severe forms of human periodontitis.http://www.sciencedirect.com/science/article/pii/S0020653923000898LoricrinPeriodontal diseaseEpithelial barrierStat6VT
spellingShingle Raisa Queiroz Catunda
Karen Ka-yan Ho
Srushti Patel
Christopher Bryant Roy
Maria Alexiou
Liran Levin
Benjamin J. Ulrich
Mark H. Kaplan
Maria Febbraio
Loricrin and Cytokeratin Disorganisation in Severe Forms of Periodontitis
International Dental Journal
Loricrin
Periodontal disease
Epithelial barrier
Stat6VT
title Loricrin and Cytokeratin Disorganisation in Severe Forms of Periodontitis
title_full Loricrin and Cytokeratin Disorganisation in Severe Forms of Periodontitis
title_fullStr Loricrin and Cytokeratin Disorganisation in Severe Forms of Periodontitis
title_full_unstemmed Loricrin and Cytokeratin Disorganisation in Severe Forms of Periodontitis
title_short Loricrin and Cytokeratin Disorganisation in Severe Forms of Periodontitis
title_sort loricrin and cytokeratin disorganisation in severe forms of periodontitis
topic Loricrin
Periodontal disease
Epithelial barrier
Stat6VT
url http://www.sciencedirect.com/science/article/pii/S0020653923000898
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