title: Porphyromonas gingivalis infection exacerbates the onset of rheumatoid arthritis in SKG mice.
abstract: Epidemiological studies have linked periodontitis to rheumatoid arthritis (RA). Porphyromonas gingivalis (Pg) was reported recently to produce citrullinated protein (CP) and increase anti-cyclic CP antibody (ACPA), both of which have been identified as causative factors of RA. In the present study, we determined the effects of Pg infection on the exacerbation of RA in a mouse model. RA model mice (SKG mice) were established by an intraperitoneal (i.p.) injection of laminarin (LA). Mice were divided into six groups, Ctrl (PBS injection), LA (LA injection), Pg/LA (Pg + LA injection), Pg (Pg injection), Ec/LA (Escherichia coli and LA injection) and Ec (E. coli injection). In order to evaluate RA, joint swelling by the arthritis score, bone morphology by microcomputed tomography (microCT), haematoxylin and eosin staining, ACPA, matrix metalloproteinase-3 (MMP-3) and cytokine level in serum by enzyme-linked immunosorbent assay were determined. Osteoclast differentiation from bone marrow mononuclear cells (BMCs) was examined to clarify the underlying mechanisms of RA. The presence of Pg and CP in joint tissue was also investigated. The arthritis score was threefold higher in the Pg/LA group than in the LA group. Severe bone destruction was observed in joint tissue of the Pg/LA group. A microCT analysis of the Pg/LA group revealed a decrease in bone density. ACPA, MMP-3, interleukin (IL)-2, IL-6, CXCL1 and macrophage inflammatory protein (MIP)-1α levels from the Pg/LA group were the highest. The osteoclastogenesis of BMCs was enhanced in the Pg/LA group. Furthermore, large amounts of Pg components and CP were detected in the Pg/LA group. In conclusion, Pg infection has the potential to exacerbate RA.
authors.affiliation: Department of Periodontal Medicine, Division of Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University.
authors.forename: M
authors.initials: M
authors.lastname: Yamakawa
authors.affiliation: Department of Periodontal Medicine, Division of Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University. kouhara@hiroshima-u.ac.jp.
authors.forename: K
authors.initials: K
authors.lastname: Ouhara
authors.affiliation: Department of Periodontal Medicine, Division of Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University.
authors.forename: M
authors.initials: M
authors.lastname: Kajiya
authors.affiliation: Department of Periodontal Medicine, Division of Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University.
authors.forename: S
authors.initials: S
authors.lastname: Munenaga
authors.affiliation: Department of Periodontal Medicine, Division of Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University.
authors.forename: M
authors.initials: M
authors.lastname: Kittaka
authors.affiliation: Department of Clinical Immunology and Rheumatology, Hiroshima University Hospital, Hiroshima, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Yamasaki
authors.affiliation: Department of Periodontal Medicine, Division of Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University.
authors.forename: K
authors.initials: K
authors.lastname: Takeda
authors.affiliation: Department of Periodontal Medicine, Division of Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University.
authors.forename: K
authors.initials: K
authors.lastname: Takeshita
authors.affiliation: Department of Periodontal Medicine, Division of Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University.
authors.forename: N
authors.initials: N
authors.lastname: Mizuno
authors.affiliation: Department of Periodontal Medicine, Division of Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University.
authors.forename: T
authors.initials: T
authors.lastname: Fujita
authors.affiliation: Department of Clinical Immunology and Rheumatology, Hiroshima University Hospital, Hiroshima, Japan.
authors.forename: E
authors.initials: E
authors.lastname: Sugiyama
authors.affiliation: Department of Periodontal Medicine, Division of Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University.
authors.forename: H
authors.initials: H
authors.lastname: Kurihara
mesh_terms: D000818:Animals; D000843:Ankle Joint / Q000000981:diagnostic imaging / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging / Q000209:etiology* / Q000473:pathology*; D016866:Bacteroidaceae Infections / Q000150:complications* / Q000382:microbiology*; D015415:Biomarkers; D002454:Cell Differentiation; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D015870:Gene Expression; D051379:Mice; D010010:Osteoclasts / Q000166:cytology / Q000378:metabolism; D016966:Porphyromonas gingivalis; D055114:X-Ray Microtomography
chemical_list: D015415:Biomarkers; D016207:Cytokines
keywords: Porphyromonas gingivalis; anti-CCP; citrullinated protein; periodontitis; rheumatoid arthritis