Session Title: Rheumatoid Arthritis - Animal Models I
Session Type: Abstract Submissions (ACR)
Background/Purpose: Periodontitis (PD) is a chronic immunoinflammatory disease caused by complex subgingival periodontal bacteria. Rheumatoid Arthritis (RA) and PD both are chronic inflammatory disorders characterized by deregulation of the host inflammatory response. Both disease share risk factors and have pathological pathways in common, resulting in soft and hard tissue destruction of synovium and periodontium, respectively. In this study, we utilize an established murine PD model induced by chronic polybacterial infection of three major human periodontal bacterial pathogens: P. gingivalis, T. denticola, and T. forsythia. Our study was designed to examine whether the induction of PD enhance arthritis in the collagen-induced arthritis (CIA) mouse model.
Methods: CIA-prone major histocompatibility congenic B10 RIII mice were used in the study. These were divided into four groups (n=10 each). Group I mice were infected orally with a polybacterial mixture of P. gingivalis, T. denticola, T. forsythia for 24 weeks. Mice in group II were also orally infected with a polybacterial mixture followed by administration of collagen II (CII) emulsified in complete Freund’s adjuvant (CFA) and boosted with CII in incomplete Freund’s adjuvant (IFA) to induce arthritis. Group III mice were sham-infected controls. Group IV mice were administered CII emulsified in CFA and IFA as collagen control. After 24 weeks of infection, mice were examined for development of PD as well as for RA clinical signs; systemic spread of the infection, matrix metalloproteinase 3 (MMP3) levels, cytokine expression, anti-CCP (cyclic citrullinated peptide) antibodies, and autoimmune signaling molecules. Further, the tissue sections from mouse ankle joints and paws were evaluated for the presence of periodontal bacteria by fluorescence in situ hybridization (FISH).
Results: Group I and II showed oral colonization/infection with all 3 bacteria (100%), higher levels of anti-bacteria IgG antibodies (P < 0.0005) and greater significant alveolar bone resorption (P < 0.0005) than the sham-infected (Group III) and collagen control mice (Group IV). Group II mice showed exacerbated clinical signs of arthritis (10/10), systemic spread of periodontal bacteria, and significant serum MMP3 levels (P < 0.05) compared to Group IV. In vivo tomographic imaging of infected+collagen treated mice using MMP3 fluorescent probe showed intense MMP3 activity (fluorescence intensity=12) in arthritic lesions (4/4) compared to collagen control mice (fluorescence intensity=5). Histopathology of infected+collagen treated mouse ankle joints showed higher levels of characteristic inflammatory cellular infiltration, destruction of articular cartilage, pannus formation, and bone distortion (6/6) compared to collagen control mice. FISH showed the presence of P. gingivalis in the ankle joints of infected+collagen treated mice.
Conclusion: This is the first study to examine a causal relationship between PD and RA using two established disease models in mice. This study provides direct evidence for a causal association between major periodontal pathogens/PD and increased severity in induced arthritis.
S. J. Calise,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/active-invasion-of-periodontal-bacteria-into-synovial-joint-exacerbates-collagen-induced-arthritis-in-disease-prone-b10-riii-mice/