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Amplifying elements of arthritis and joint destruction
  1. Wim B van den Berg,
  2. Peter L van Lent,
  3. Leo A B Joosten,
  4. Shahla Abdollahi-Roodsaz,
  5. Marije I Koenders
  1. Rheumatology Research and Advanced Therapeutics, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
  1. Wim B van den Berg, Rheumatology Research and Advanced Therapeutics, Radboud University Nijmegen Medical Center, Geert Grooteplein 26, 6525 GA Nijmegen, The Netherlands; w.vandenberg{at}reuma.umcn.nl

Abstract

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterised by chronic joint inflammation and variable degrees of bone and cartilage erosion. Studies in animal models of arthritis provide insight into elements which can amplify destructive features. The presence of immune complexes in the joint makes arthritis more erosive. Although considerable bone erosion still occurs in the absence of FcγR triggering by immune complexes, through cytokine-induced RANKL and direct osteoclast activation, cartilage erosion is heavily dependent on the FcγR pathway. T cell factors such as IFNγ and IL17 further amplify erosion through upregulation of the damaging FcγRI and stimulation of the influx of granulocytes, respectively. Apart from immune elements, environmental pressure and components of tissue damage contribute through innate pathways. Spontaneous T cell-dependent arthritis in IL1Ra–/– mice is absent under germ-free conditions, and markedly suppressed in TLR4-deficient mice. Moreover, TLR4 blocking with a receptor antagonist suppresses erosive arthritis.

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Footnotes

  • Competing interests: None declared.

  • Abbreviations:
    CCP
    citrullinated protein
    FcγR
    Fcγ receptors
    GPI, glucose phosphate isomerase; IC, immune complex; MMPs
    matrix metalloproteinases
    OPG, osteoprotegerin; RA
    rheumatoid arthritis
    TLR
    toll-like receptor
    TNFtg
    TNF transgenic

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