Porphyromonas gingivalis experimentally induces periodontis and an anti-CCP2-associated arthritis in the rat

• Published in: Annals of the rheumatic diseases Vol. 78; no. 5; pp. 594 - 599
• Main Authors: Courbon, Guillaume, Rinaudo-Gaujous, Mélanie, Blasco-Baque, Vincent, Auger, Isabelle, Caire, Robin, Mijola, Lambert, Vico, Laurence, Paul, Stéphane, Marotte, Hubert
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group Ltd and European League Against Rheumatism 01.05.2019; Elsevier Limited; BMJ Publishing Group
• Subjects: ACPA; aetiology; Animals; Ankle; Ankle - pathology; Anti-Citrullinated Protein Antibodies - blood; Anti-Citrullinated Protein Antibodies - immunology; arthritis; Arthritis, Experimental - immunology; Arthritis, Experimental - microbiology; Autoantibodies - blood; Bacteria; Biomarkers - blood; Bone loss; Bone resorption; Chemokines; Citrulline; Computed tomography; Cortical bone; Gingivitis; Gum disease; Human health and pathology; Immunoglobulins; Immunology; Infectious diseases; Inflammation; Inflammation Mediators - blood; Joint diseases; Laboratory animals; Life Sciences; Microbiology and Parasitology; Peptides; Peptides, Cyclic - blood; Peptides, Cyclic - immunology; Periodontal diseases; periodontitis; Periodontitis - immunology; Periodontitis - microbiology; Pharmaceutical sciences; Pharmacology; Porphyromonas gingivalis; Prevotella; Proteins; Rats; Rats, Inbred Lew; Rheumatoid arthritis; Serology; Tumor necrosis factor-TNF; Vaccinology; Virology; aetiology; arthritis; ACPA; bone loss; periodontitis
• ISSN: 0003-4967; 1468-2060; 1468-2060
• DOI: 10.1136/annrheumdis-2018-213697

ObjectivesAssociation 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.MethodsLewis 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.ResultsPD 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.ConclusionsIn 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.