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Porphyromonas gingivalis experimentally induces periodontis and an anti-CCP2-associated arthritis in the rat
  1. Guillaume Courbon1,
  2. Mélanie Rinaudo-Gaujous1,2,3,
  3. Vincent Blasco-Baque4,5,6,7,
  4. Isabelle Auger8,
  5. Robin Caire1,
  6. Lambert Mijola1,9,
  7. Laurence Vico1,
  8. Stéphane Paul2,3,
  9. Hubert Marotte1,9
  1. 1 SAINBIOSE, INSERM U1059, University of Lyon, Saint-Etienne, France
  2. 2 Laboratory of Immunology and Immunomonitoring, University Hospital of Saint-Etienne, Saint-Etienne, France
  3. 3 GIMAP EA3064, University of Lyon, Saint-Etienne, France
  4. 4 INSERM U1048, Toulouse, France
  5. 5 Unité Mixte de Recherche, Institut de Maladies Métaboliques et Cardiovasculaires (I2MC), Université Paul Sabatier (UPS), Toulouse, France
  6. 6 Faculté de Chirurgie Dentaire de Toulouse, Université Paul Sabatier, Toulouse, France
  7. 7 CHU Toulouse, Service Odontologie, Toulouse, France
  8. 8 INSERM UMR 1097, Aix Marseille University, Marseille, France
  9. 9 Department of Rheumatology, University Hospital of Saint-Etienne, Saint-Etienne, France
  1. Correspondence to Professor Hubert Marotte, Department of Rheumatology, University Hospital of Saint-Etienne, Saint-Etienne 42055, France; hubert.marotte{at}chu-st-etienne.fr

Abstract

Objectives Association between periodontal disease (PD) and rheumatoid arthritis (RA) has been extensively described, but direct evidence of causal involvement of PD in RA is missing. We investigated the priming role of oral Porphyromonas gingivalis (P. gingivalis) in PD and subsequent RA and we assessed biomarkers of bone resorption and arthritis development in rats.

Methods Lewis rats were orally exposed to either P. gingivalis, Prevotella intermedia or control gel for 1 month and then followed for 8 months. The onset and development of PD was assessed by serology, gingivitis severity and micro-CT (µCT). We investigated arthritis development using circulating proinflammatory markers, anticyclic citrullinated peptide (CCP), anticitrullinated protein antibody (ACPA), ankle histology and µCT.

Results PD was only observed in the P. gingivalis treated rats, as early as 1 month postexposure. Joint and systemic inflammation were detected only in the P. gingivalis group after 4 and 8 months. At 8 months, inflammatory cell infiltrate was observed in ankle joints and paralleled cortical erosions and overall cortical bone reduction. Furthermore, anti-CCP2 correlated with local and systemic bone loss.

Conclusions In our long-term study, PD induced by oral exposure to P. gingivalis triggered seropositive arthritis, with systemic inflammation and bone erosions. This is the first in vivo demonstration of arthritis induced by oral priming with P. gingivalis.

  • arthritis
  • periodontitis
  • bone loss
  • ACPA
  • aetiology

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Footnotes

  • Handling editor Josef S Smolen

  • Contributors GC, MRG, VBB, SP and HM designed the study. GC, MRG, IA and RC performed the experiments. GC, LM, IA, SP and HM analysed the data. GC and HM wrote the manuscript. All authors approved the final version.

  • Funding This work was funded by Aide à la Recherche médicale de proximité (AIRE) and Aide à la Recherche Médicale Ondaine et Environs.

  • Competing interests HM reports grants, personal fees and non-financial support from Pfizer, grants, personal fees and non-financial support from AbbVie, grants, non-financial support and other from Nordic Pharma, grants, personal fees and non-financial support from MSD, grants and other from UCB, personal fees and non-financial support from BMS, personal fees, non-financial support and other from Novartis, personal fees from Roche Chugai, personal fees from Janssen, personal fees from Biogen, personal fees from Biogaran, grants, personal fees and other from Sanofi, outside the submitted work.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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