Effects by periodontitis on pristane-induced arthritis in rats

Abstract

BackgroundAn infection-immune association of periodontal disease with rheumatoid arthritis has been suggested. This study aimed to investigate the effect of pre-existing periodontitis on the development and the immune/inflammatory response of pristane-induced arthritis.MethodsWe investigated the effect of periodontitis induced by ligature placement and Porphyromonas gingivalis (P. gingivalis) infection, in combination with Fusobacterium nucleatum to promote its colonization, on the development of pristane-induced arthritis (PIA) in rats (Dark Agouti). Disease progression and severity of periodontitis and arthritis was monitored using clinical assessment, micro-computed tomography (micro-CT)/intraoral radiographs, antibody response, the inflammatory markers such as α-1-acid glycoprotein (α-1-AGP) and c-reactive protein (CRP) as well as cytokine multiplex profiling at different time intervals after induction.ResultsExperimentally induced periodontitis manifested clinically (P < 0.05) prior to pristane injection and progressed steadily until the end of experiments (15 weeks), as compared to the non-ligated arthritis group. Injection of pristane 8 weeks after periodontitis-induction led to severe arthritis in all rats demonstrating that the severity of arthritis was not affected by the pre-existence of periodontitis. Endpoint analysis showed that 89% of the periodontitis-affected animals were positive for antibodies against arginine gingipain B and furthermore, the plasma antibody levels to a citrullinated P. gingivalis peptidylarginine deiminase (PPAD) peptide (denoted CPP3) were significantly (P < 0.05) higher in periodontitis rats with PIA. Additionally, there was a trend towards increased pro-inflammatory and anti-inflammatory cytokine levels, and increased α-1-AGP levels in plasma from periodontitis-challenged PIA rats.ConclusionsPre-existence of periodontitis induced antibodies against citrullinated peptide derived from PPAD in rats with PIA. However, there were no differences in the development or severity of PIA between periodontitis challenged and periodontitis free rats.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-016-1067-6) contains supplementary material, which is available to authorized users.

Periodontal Health and Oral Microbiota in Patients with Rheumatoid Arthritis

“…For the qPCR analysis of subgingival plaque samples, two sets of primers were used for bacteria detection, one species-specific pair for P. gingivalis and the other pair targeting the bacterial 16S rRNA gene [34,35]. The qPCR analyses were performed as described in the Supplementary Methods (Quantitative Polymerase Chain Reaction, qPCR).…”

Rheumatoid Arthritis-Associated Mechanisms of Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans

“…Using models of arthritis in rats, periodontitis induced by P. gingivalis had no effect in the development or severity of pristane-induced arthritis in Dark Agouti rats [143]. More recently, however, one study showed that P. gingivalis -associated periodontitis was sufficient to induce erosive arthritis in Lewis rats, providing the first direct evidence that P. gingivalis may have the capacity to induce arthritis [144].…”

“…Several mechanisms have been proposed by which P. gingivalis may promote autoimmune arthritis in humans and in experimental animals. These include the induction of a systemic Th17 cell response [132,133,134], induction of autoantibodies [131,138,143,144], cross-reactivity between bacterial and host antigens [145], by promoting C5a generation [141], through direct dissemination of P. gingivalis into the joints [136], and by swallowing the bacteria, which may alter the gut microbiota and gut immune system [137]. Nevertheless, the production of citrullinated autoantigens by a PAD enzyme released from P. gingivalis is considered the most important mechanistic evidence to support a role of P. gingivalis in RA pathogenesis [14,146].…”

“…Nevertheless, antibodies to CPPs are still being used as biomarkers to link PPAD self-endocitrullination and RA pathogenesis. In particular, serum reactivity against the peptide termed CPP3 has been used to define clinical associations between P. gingivalis and RA [122,123,163,164], and to demonstrate that P. gingivalis can induce antibodies to citrullinated PPAD in rats [143]. Since the significance of CPPs is unclear, the findings generated with these peptides should be taken with caution.…”

Bisleuconothine A protects periodontal tissue via the regulation of RANKL expression and infiltration of inflammatory cells

“…Periodontitis was induced in the rats using standard procedures [15]. The rats were anesthetized via intraperitoneal administration of 50 mg/kg bwt pentobarbital and a suture was made around each cervix of the first molar (M1) on bilateral sides in the maxilla in the open mouth, using Hashimoto's gag.…”