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SAT0062 Blockade of connective tissue growth factor (CTGF) ameliorates murine model of rheumatoid arthritis
  1. K. Nozawa1,
  2. M. Fujishiro2,
  3. M. Kawasaki2,
  4. A. Yamaguchi1,
  5. K. Ikeda3,
  6. S. Morimoto3,
  7. N. poh-Sing4,
  8. Y. Kato4,
  9. M. Asano5,
  10. I. Sekigawa3,
  11. Y. Takasaki1
  1. 1Department of Rheumatology, Juntendo University School of Medicine, Tokyo
  2. 2Institute for Environment and Gender Specific Medicine, Juntendo University Graduate School of Medicine
  3. 3Department of Rheumatology, Juntendo University Urayasu Hospital, Chiba
  4. 4Nihon Nosan Corporation, Kanagawa
  5. 5Internal midicine, Toubu-chiiki Hospital, Tokyo, Japan

Abstract

Background Our previous study demonstrated changes in the profiles of serum protein biomarkers in infliximab-treated rheumatoid arthritis (RA) patients using a novel approach to proteomic research (1). Several proteins exhibited vast changes in expression after infliximab treatment, and we have reported connective tissue growth factor (CTGF) appeared to be a potent strong biomarker in infliximab-treated RA patients (1). Furthermore, we also found that CTGF was upregulated in both serum level and tissue expression of patients with RA, and that CTGF was related to disease progression of RA through abnormal activation of osteoclasts in vitro (2). To extend our research project, this study was conducted to clarify roles of CTGF for RA pathogenesis using murine collagen-induced arthritis (CIA) model.

Objectives We have shown that connective tissue growth factor (CTGF) was excessively produced in synovial tissue of rheumatoid arthritis (RA) and played an important role for pathogenesis of RA through inducing abnormal osteoclasts activation. To investigate more precise roles of CTGF for RA pathogenesis, we analyzed effects of blockade against CTGF pathway on the progression of arthritis in collagen induced arthritis (CIA) mouse.

Methods CIA was introduced in DBA/1J mice by immunization in combination with type II collagen and complete Freund’s adjuvant (CFA). The efficacy for prevention of progression of the arthritis was evaluated in the CIA mice treated with or without neutralizing anti-CTGF monoclonal antibody (mAb).

Results The blockade of CTGF by anti-CTGF mAb treatment significantly ameliorated the arthritis compared to the non-treated controls. Moreover, serum levels of C reactive protein (CRP) and matrix metalloproteinase (MMP)-3 reduced in the CTGF-treated mice. The blockade of CTGF reduced a number of osteoclasts in inflamed synovial tissue and inhibited antigen specific T lymphocytes proliferation against type II collagen stimulation. Moreover, the blockade of CTGF decreased interleukin-17 (IL-17) production from purified CD4+ T lymphocytes.

Conclusions The present study demonstrated that the blockade of CTGF significantly prevented a progression of arthritis in CIA mice. In pathogenesis of the arthritis in CIA mice, CTGF was considered to be associated with abnormal osteoclastic activation. Furthermore, CTGF possessed a functional property of promoting Th17 differentiation in CIA mice and appeared to have also proliferative effect on antigen specific response on the progression for arthritis.

  1. Sekigawa I, Yanagida M, Iwabuchi K, Kaneda K, Kaneko H, Takasaki Y, Jung G, Sone S, Tanaka Y, Ogawa H, Takamori K. Protein biomarker analysis by mass spectrometry in patients with rheumatoid arthritis receiving anti-tumor necrosis factor-alpha antibody therapy. Clin Exp Rheumatol. 2008 Mar-Apr;26(2):261-7.

  2. Nozawa K, Fujishiro M, Kawasaki M, Kaneko H, Iwabuchi K, Yanagida M, Suzuki F, Miyazawa K, Takasaki Y, Ogawa H, Takamori K, Sekigawa I. Connective tissue growth factor promotes articular damage by increased osteoclastogenesis in patients with rheumatoid arthritis. Arthritis Res Ther. 2009;11(6):R174.

Disclosure of Interest None Declared

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