Interplay between P. gingivalis, F. nucleatum and A. actinomycetemcomitans in murine alveolar bone loss, arthritis onset and progression.

Increasing evidence supports the association of periodontitis with rheumatoid arthritis. Even though a prominent role has been postulated for Porphyromonas gingivalis, many bacterial species contribute to the pathogenesis of periodontal disease. We therefore investigated the impact of Porphyromonas gingivalis as well as other major pathobionts on the development of both, periodontitis and arthritis in the mouse. Pathobionts used - either alone or in combination - were Porphyromonas gingivalis, Fusobacterium nucleatum and Aggregatibacter actinomycetemcomintans. Periodontitis was induced via oral gavage in SKG, DBA/1 and F1 (DBA/1 × B10.Q) mice and collagen-induced arthritis was provoked via immunization and boost with bovine collagen type II. Alveolar bone loss was quantified via micro computed tomography, arthritis was evaluated macroscopically and histologically and serum antibodies were assessed. Among the strains tested, only F1 mice were susceptible to P. gingivalis induced periodontitis and showed significant alveolar bone loss. Bone loss was paralleled by antibody titers against P. gingivalis. Of note, mice inoculated with the mix of all three pathobionts showed less alveolar bone loss than mice inoculated with P. gingivalis alone. However, oral inoculation with either F. nucleatum or A. actinomycetemcomintans alone accelerated subsequent arthritis onset and progression. This is the first report of a triple oral inoculation of pathobionts combined with collagen-induced arthritis in the mouse. In this interplay and this particular genetic setting, F. nucleatum and A. actinomycetemcomitans exerted a protective impact on P. gingivalis induced alveolar bone loss. By themselves they did not induce periodontitis yet accelerated arthritis onset and progression.