PMID- 27465496 OWN - NLM STAT- MEDLINE DCOM- 20170428 LR - 20181113 IS - 1365-2249 (Electronic) IS - 0009-9104 (Print) IS - 0009-9104 (Linking) VI - 186 IP - 2 DP - 2016 Nov TI - Porphyromonas gingivalis infection exacerbates the onset of rheumatoid arthritis in SKG mice. PG - 177-189 LID - 10.1111/cei.12847 [doi] AB - 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)-1alpha 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. CI - (c) 2016 British Society for Immunology. FAU - Yamakawa, M AU - Yamakawa M AD - Department of Periodontal Medicine, Division of Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University. FAU - Ouhara, K AU - Ouhara K AD - Department of Periodontal Medicine, Division of Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University. kouhara@hiroshima-u.ac.jp. FAU - Kajiya, M AU - Kajiya M AD - Department of Periodontal Medicine, Division of Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University. FAU - Munenaga, S AU - Munenaga S AD - Department of Periodontal Medicine, Division of Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University. FAU - Kittaka, M AU - Kittaka M AD - Department of Periodontal Medicine, Division of Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University. FAU - Yamasaki, S AU - Yamasaki S AD - Department of Clinical Immunology and Rheumatology, Hiroshima University Hospital, Hiroshima, Japan. FAU - Takeda, K AU - Takeda K AD - Department of Periodontal Medicine, Division of Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University. FAU - Takeshita, K AU - Takeshita K AD - Department of Periodontal Medicine, Division of Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University. FAU - Mizuno, N AU - Mizuno N AD - Department of Periodontal Medicine, Division of Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University. FAU - Fujita, T AU - Fujita T AD - Department of Periodontal Medicine, Division of Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University. FAU - Sugiyama, E AU - Sugiyama E AD - Department of Clinical Immunology and Rheumatology, Hiroshima University Hospital, Hiroshima, Japan. FAU - Kurihara, H AU - Kurihara H AD - Department of Periodontal Medicine, Division of Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University. LA - eng PT - Journal Article DEP - 20160829 PL - England TA - Clin Exp Immunol JT - Clinical and experimental immunology JID - 0057202 RN - 0 (Biomarkers) RN - 0 (Cytokines) SB - IM MH - Animals MH - Ankle Joint/diagnostic imaging/pathology MH - Arthritis, Rheumatoid/diagnostic imaging/*etiology/*pathology MH - Bacteroidaceae Infections/*complications/*microbiology MH - Biomarkers MH - Cell Differentiation MH - Cytokines/metabolism MH - Disease Models, Animal MH - Disease Progression MH - Female MH - Gene Expression MH - Mice MH - Osteoclasts/cytology/metabolism MH - *Porphyromonas gingivalis MH - X-Ray Microtomography PMC - PMC5054573 OTO - NOTNLM OT - Porphyromonas gingivalis OT - anti-CCP OT - citrullinated protein OT - periodontitis OT - rheumatoid arthritis EDAT- 2016/07/29 06:00 MHDA- 2017/04/30 06:00 PMCR- 2017/11/01 CRDT- 2016/07/29 06:00 PHST- 2016/07/25 00:00 [accepted] PHST- 2016/07/29 06:00 [pubmed] PHST- 2017/04/30 06:00 [medline] PHST- 2016/07/29 06:00 [entrez] PHST- 2017/11/01 00:00 [pmc-release] AID - CEI12847 [pii] AID - 10.1111/cei.12847 [doi] PST - ppublish SO - Clin Exp Immunol. 2016 Nov;186(2):177-189. doi: 10.1111/cei.12847. Epub 2016 Aug 29.