Abstract
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.
Highlights
Rheumatoid arthritis (RA) is a chronic autoimmune disease that primarily affects the joints but can turn into a systemic disorder involving the heart, the eyes, the gastrointestinal tract, the lungs, the kidneys and the nervous system[1,2]
PD was assessed by measuring the distance from the cemento-enamel junction (CEJ) to the alveolar bone crest (ABC) and calculating the bone loss by comparing the P. gingivalis-inoculated mice to their untreated controls (n = 5 per strain)
We had postulated upfront that periodontitis (PD) following oral inoculation with P. gingivalis is dependent on a susceptible genetic background
Summary
Rheumatoid arthritis (RA) is a chronic autoimmune disease that primarily affects the joints but can turn into a systemic disorder involving the heart, the eyes, the gastrointestinal tract, the lungs, the kidneys and the nervous system[1,2]. RA will lead to irreversible damage and functional loss of the joints and to comorbidity[3] This disease is multifactorial with genetic as well as environmental factors triggering its pathogenesis[4]. Recent explanations for the association of RA with PD include specific immune modulations and altered gut microbioms due to oral dysbiosis[13] Research into this association gained further momentum by two observations, the first one being that antibodies against citrullinated peptide antigens (ACPA) are highly specific for RA and precede the onset of the disease by several years[14] and second, that P. gingivalis is so far the only oral pathobiont that was proven to be capable of citrullination[15]. We postulated that (i) PD as a consequence of oral inoculation with a certain pathobiont is dependent on the genetic background, (ii) the combination of three different and aggressive pathobionts will aggravate PD and (iii) the more severe the preexisting PD, the more exacerbated the subsequent arthritis
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