Session Type: ACR Poster Session A
Session Time: 9:00AM-11:00AM
Periodontal disease (PD) is the chronic inflammatory disease caused by the infection of periodontopathogenic bacteria, Porphyromonas gingivalis (Pg). Pg infection is known as major pathogenic factor of some systemic diseases including rheumatoid arthritis (RA). Our group established b-gulcan (laminarin, LA) induced RA model mouse with Pg infection (Pg-RA mouse) by using SKG mouse. Pg-RA mouse showed severe arthritis and joint destruction like human RA compared with RA mouse. The cause of exacerbation of joint destruction by Pg infection was the activation of osteoclastogenesis (OCD) in Pg-RA mouse with the elevation of ACPA, IL-6, and MMP-3 in serum (Clin Exp Immunol. 2016 Nov;186(2):177-189.). Immune complex (IC) is also important in the activation of OCD. However, the involvement of IC derived from citrullinated protein (CP) in the progression of OCD is unclear. It is also unclear that the involvement of Pg pathogenic factors even if there are some enzymes possessed by Pg such as peptidyl arginine diamidase (PAD) and gingipain. In this study, the involvement of Pg which is major source of endogeneous CP in bacteria in the synthesis of IC in the periodontal tissue and joint tissue was determined. The localization and effect of ACPA in the progression of RA in model mouse were also analyzed by using a ACPA monoclonal antibody generated from RA patientfs B cell (CCP1-Ab).
In order to induce periodontal bone loss in SKG mouse, Pg was diluted into 2% carboxyl methyl cellulose (CMC, 10f8 CFU/50 ml) and also infected into mouse oral cavity twice a week for 2 weeks with the placement of 5-0 silk thread around the maxillary second molar. As a control, CMC was only applied into oral cavity. At the same time for induction of RA, the single i.p. injection of LA was performed. In order to measure the amount of CP and ACPA, mouse was received adaptive transferred CCP-Ab1 (Arthritis Rheumatol. 2015 May;67(8):2020-31.). Then, the tissue homogenates of periodontal tissue, joint tissue, spleen and serum were determined by ELISA. The immune fluorescence microscopic analysis was also performed to determine the localization of ACPA and IC in periodontal tissue. In order to determine the effect of ACPA in the activation of OCD, bone marrow mononuclear cell (BMC) was cultured with sRANKL and M-CSF in the presence or absence of CCP-Ab1 and analyzed by TRAP staining and by CellInsight CX-5 HCS Platform for quantitative analysis of osteoclast. mRNA expression of OCD related genes in BMC was determined by quantitative RT-PCR.
Results: and Conclusion:
The distributions of ACPA in periodontal tissue, joint tissue, and spleen were observed in Pg infected periodontitis mouse by ELISA. IC was also generated in Pg infected periodontitis mouse compared with healthy mouse. The adaptive transfer of CCP1-Ab resulted in the elevation of AS compared with the that of control IgG. OCD was activated in the presence of CCP1-Ab compared with control antibody. mRNA expression of OCD related gene (traf6, nfatc1, Oscar, dc-stamp, mmp-9, and catK) in BMC was induced by CCP1-Ab. The possibility of the involvement of IC from ACPA and CP generated by Pg in periodontal tissue for the progression of bone resorption was observed in Pg-RA mouse.
To cite this abstract in AMA style:Ouhara K, Ozawa T, Munnaga S, Kuranobu T, Hamamoto Y, Kawai T, Sugiyama E, Kurihara H. A Human ACPA Monoclonal Antibody Is Preferably Localized at Inflammatory Gingival Tissue and Activates Osteoclastogenensis in Porphyromonas Gingivalis Infected SKG Mouse [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 10). https://acrabstracts.org/abstract/a-human-acpa-monoclonal-antibody-is-preferably-localized-at-inflammatory-gingival-tissue-and-activates-osteoclastogenensis-in-porphyromonas-gingivalis-infected-skg-mouse/. Accessed June 2, 2020.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/a-human-acpa-monoclonal-antibody-is-preferably-localized-at-inflammatory-gingival-tissue-and-activates-osteoclastogenensis-in-porphyromonas-gingivalis-infected-skg-mouse/