Abstract

Epidemiological studies show an association between rheumatoid arthritis (RA) and periodontal disease. Porphyromonas gingivalis (P.gingivalis) is a well-known pathogen in periodontitis. This study investigated the pathogenic effects of P.gingivalis on autoimmune arthritis in vivo. Collagen-induced arthritis (CIA) mice were intraperitoneally injected with W83 and 2561 strains of P.gingivalis. Infection with P.gingivalis exacerbated arthritis score in CIA mice. Synovial inflammation and bone destruction in CIA mice infected with P.gingivalis were more severe than in uninfected CIA mice. Both W83 and 2561 strains were more pro-arthritic after arthritis symptom was fully activated. Interestingly, only W83 strain was arthritogenic before autoimmune reaction initiated. Citrullination was detected in synovial tissue of CIA mice and CIA mice inoculated with P.gingivalis, but not in normal control mice. The citrullinated area was greater in P.gingivalis-infected CIA mice than in non-infected CIA mice. This study showed that P.gingivalis exacerbated disease in a mouse model of autoimmune arthritis and increased the expression of citrullinated antigens in the synovium. The arthritogenic effects of P.gingivalis were at least in part, dependent upon the bacterial strain with or without fimbriae expression, route and time of infection. P.gingivalis-mediated citrullination may explain the possible link between periodontal disease and RA.

Highlights

  • Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by joint inflammation and destruction [1]

  • Since Peptidylarginine deaminase (PAD) involves in biological processes such as epidermal differentiation, hair follicles maturation, and other epigenetic regulations, it is reported to be related to diseases such as psoriasis or multiple sclerosis

  • We investigated whether P.gingivalis infection affects the incidence or severity of collagen-induced arthritis (CIA)

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Summary

Introduction

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by joint inflammation and destruction [1]. Production of rheumatoid factor and autoantibodies leads to increased functional disability and morbidity [2]. Citrullination is an important post-translational modification that is ubiquitous in normal physiology. It is a process which arginine is conversed into citrulline in proteins. PAD enzymes are normally involved in various regulatory processes in human [8,9]. Since PAD involves in biological processes such as epidermal differentiation, hair follicles maturation, and other epigenetic regulations, it is reported to be related to diseases such as psoriasis or multiple sclerosis

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