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Arthritis Research & Therapy
Published in: Arthritis Research & Therapy 1/2018

Open Access 01-12-2018 | Research article

The involvement of C5a in the progression of experimental arthritis with Porphyromonas gingivalis infection in SKG mice

Authors: Syuichi Munenaga, Kazuhisa Ouhara, Yuta Hamamoto, Mikihito Kajiya, Katsuhiro Takeda, Satoshi Yamasaki, Toshihisa Kawai, Noriyoshi Mizuno, Tsuyoshi Fujita, Eiji Sugiyama, Hidemi Kurihara

Published in: Arthritis Research & Therapy | Issue 1/2018

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Abstract

Background

Epidemiological evidence to suggest that periodontal disease (PD) is involved in the progression of rheumatoid arthritis (RA) is increasing. The complement system plays a critical role in immune responses. C5a has been implicated in chronic inflammatory diseases, including PD and RA. Porphyromonas gingivalis is the major causative bacteria of PD and can produce C5a. Therefore, it is hypothesized that P. gingivalis infection is involved in the progression of RA by elevating C5a levels. In the present study, P. gingivalis–infected RA model mice were established to investigate the involvement of C5a.

Methods

SKG mice orally infected with P. gingivalis were immunized with intraperitoneal injection of laminarin (LA) to induce arthritis. Arthritis development was assessed by arthritis score (AS), bone destruction on the talus, histology, and serum markers of RA. In order to investigate the effects of serum C5a on bone destruction, osteoclast differentiation of bone marrow mononuclear cells was examined by using serum samples from each group of mice. The relationship between C5a levels and antibody titers to periodontal pathogens in patients with RA was investigated by enzyme-linked immunosorbent assay.

Results

P. gingivalis oral infection increased AS, infiltration of inflammatory cells, bone destruction on the talus, and serum markers of RA in mice immunized with LA. The addition of serum from LA-injected mice with the P. gingivalis oral infection promoted osteoclast differentiation, and the addition of a neutralization antibody against C5a suppressed osteoclast differentiation. C5a levels of serum in RA patients with positive P. gingivalis antibody were elevated compared with those in RA patients with negative P. gingivalis antibody.

Conclusions

These results suggest that P. gingivalis infection enhances the progression of RA via C5a.
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Metadata
Title
The involvement of C5a in the progression of experimental arthritis with Porphyromonas gingivalis infection in SKG mice
Authors
Syuichi Munenaga
Kazuhisa Ouhara
Yuta Hamamoto
Mikihito Kajiya
Katsuhiro Takeda
Satoshi Yamasaki
Toshihisa Kawai
Noriyoshi Mizuno
Tsuyoshi Fujita
Eiji Sugiyama
Hidemi Kurihara
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 1/2018
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/s13075-018-1744-3

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