Porphyromonas gingivalis peptidylarginine deiminase, a key contributor in the pathogenesis of experimental periodontal disease and experimental arthritis

Neville Gully; Richard Bright; Victor Marino; Ceilidh Marchant; Melissa Cantley; David Haynes; Catherine Butler; Stuart Dashper; Eric Reynolds; Mark Bartold

doi:10.1371/journal.pone.0100838

Porphyromonas gingivalis peptidylarginine deiminase, a key contributor in the pathogenesis of experimental periodontal disease and experimental arthritis

PLoS One. 2014 Jun 24;9(6):e100838. doi: 10.1371/journal.pone.0100838. eCollection 2014.

Authors

Affiliations

¹ Colgate Australian Clinical Dental Research, School of Dentistry, University of Adelaide, Adelaide, South Australia, Australia.
² Discipline of Anatomy and Pathology, School of Medical Sciences, University of Adelaide, Adelaide, South Australia, Australia.
³ Oral Health Collaborative Research Centre, Melbourne Dental School, The University of Melbourne, Melbourne, Victoria, Australia.

Abstract

Objectives: To investigate the suggested role of Porphyromonas gingivalis peptidylarginine deiminase (PAD) in the relationship between the aetiology of periodontal disease and experimentally induced arthritis and the possible association between these two conditions.

Methods: A genetically modified PAD-deficient strain of P. gingivalis W50 was produced. The effect of this strain, compared to the wild type, in an established murine model for experimental periodontitis and experimental arthritis was assessed. Experimental periodontitis was induced following oral inoculation with the PAD-deficient and wild type strains of P. gingivalis. Experimental arthritis was induced via the collagen antibody induction process and was monitored by assessment of paw swelling and micro-CT analysis of the radio-carpal joints. Experimental periodontitis was monitored by micro CT scans of the mandible and histological assessment of the periodontal tissues around the mandibular molars. Serum levels of anti-citrullinated protein antibodies (ACPA) and P. gingivalis were assessed by ELISA.

Results: The development of experimental periodontitis was significantly reduced in the presence of the PAD-deficient P. gingivalis strain. When experimental arthritis was induced in the presence of the PAD-deficient strain there was less paw swelling, less erosive bone damage to the joints and reduced serum ACPA levels when compared to the wild type P. gingivalis inoculated group.

Conclusion: This study has demonstrated that a PAD-deficient strain of P. gingivalis was associated with significantly reduced periodontal inflammation. In addition the extent of experimental arthritis was significantly reduced in animals exposed to prior induction of periodontal disease through oral inoculation of the PAD-deficient strain versus the wild type. This adds further evidence to the potential role for P. gingivalis and its PAD in the pathogenesis of periodontitis and exacerbation of arthritis. Further studies are now needed to elucidate the mechanisms which drive these processes.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Arthritis, Experimental / complications*
Arthritis, Experimental / diagnostic imaging
Bacterial Proteins / genetics
Bacterial Proteins / physiology*
Disease Models, Animal
Enzyme-Linked Immunosorbent Assay
Hydrolases / genetics
Hydrolases / physiology*
Mice
Mice, Inbred BALB C
Periodontitis / complications
Periodontitis / diagnostic imaging
Periodontitis / etiology*
Porphyromonas gingivalis / genetics
Protein-Arginine Deiminases
Radiography

Substances

Bacterial Proteins
Hydrolases
Protein-Arginine Deiminases

Grants and funding

This study was supported in part by research grants from the Australian Dental Research Fund (ADRF 56/2010) and the National Health & Medical Council of Australia (NHMRC 1023747). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.