Periodontal bacterial colonization in synovial tissues exacerbates collagen-induced arthritis in B10.RIII mice

Abstract

BackgroundIt has been previously hypothesized that oral microbes may be an etiological link between rheumatoid arthritis (RA) and periodontal disease. However, the mechanistic basis of this association is incompletely understood. Here, we investigated the role of periodontal bacteria in induction of joint inflammation in collagen-induced arthritis (CIA) in B10.RIII mice.MethodsCIA-prone B10.RIII mice were infected orally with a polybacterial mixture of Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia for 24 weeks before induction of CIA. The ability of polybacterial mixture to colonize the periodontium and induce systemic response, horizontal alveolar bone resorption in infected B10.RIII mice was investigated. Arthritis incidence, severity of joint inflammation, pannus formation, skeletal damage, hematogenous dissemination of the infection, matrix metalloproteinase 3 (MMP3) levels, and interleukin-17 expression levels were evaluated.ResultsB10.RIII mice had gingival colonization with all three bacteria, higher levels of anti-bacterial immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies, significant alveolar bone resorption, and hematogenous dissemination of P. gingivalis to synovial joints. Infected B10.RIII mice had more severe arthritis, and higher serum matrix metalloproteinase 3 levels and activity. Histopathological analysis showed increased inflammatory cell infiltration, destruction of articular cartilage, erosions, and pannus formation. Additionally, involved joints showed had expression levels of interleukin-17.ConclusionThese findings demonstrate that physical presence of periodontal bacteria in synovial joints of B10.RIII mice with collagen-induced arthritis is associated with arthritis exacerbation, and support the hypothesis that oral bacteria, specifically P. gingivalis, play a significant role in augmenting autoimmune arthritis due to their intravascular dissemination to the joints.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-016-1056-4) contains supplementary material, which is available to authorized users.

Probiotics for the Management of Rheumatoid Arthritis

“…The study suggests that pathogenesis of RA follows in two steps: harmful subgingival bacteria first attack the host immune system in the form of periodontal disease and the resulting inflammatory conditions cause tissue damage in the form of RA. 18 These findings provide knowledge about the human microbiome and autoimmune disease that could lead to more effective treatment for both periodontal disease and RA in the future.…”

“…An epidemiological relationship may exist between the two diseases because of their similar risk factors, mechanisms for disease progression, and the fact that treatment of periodontal disease positively impacts RA severity in patients. 18 Periodontal diseases, such as periodontitis and gingivitis, are dysbiotic and polymicrobial conditions. Inflammation and tissue damage occurs when the host's innate and adaptive immune functions fail.…”

“…17 The critical Th17 cells that are present in diseased gut mucosa also appear in the sites of periodontal disease where chronic inflammation exists. 2 A murine model by Chukkapalli et al 18 found that oral bacteria exacerbate RA by infecting mice with three oral pathogens (P. gingavalis, T. denticola, and T. forsythia). These strains are common in human periodontal disease as well.…”

Reduction of Articular and Systemic Inflammation by Kava-241 in a Porphyromonas gingivalis-Induced Arthritis Murine Model

“…In patients with RA, a correlation between the presence of P. gingivalis and anti-citrullinated protein antibodies has already been observed (12). Its detrimental effect was also confirmed in vivo in several mouse models, in which P. gingivalis infection exacerbated collagen antibody (AB)-induced arthritis through different mechanisms, including modification of the gut microbiota and the associated autoimmune response (13,14), neutrophil activation (15), or induction of bone destruction (16).…”

Periodontal Disease and Autoimmunity: What We Have Learned from Microbiome Studies in Rheumatology

“…In a murine model of collagen-induced arthritis, oral infection with bacteria associated with periodontitis in humans developed exacerbated signs of inflammatory arthropathy, raised levels of matrix metalloproteinase 3 and histological evidence of active arthritis [66].…”