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Blockade of Dickkopf-1 induces fusion of sacroiliac joints
  1. Stefan Uderhardt (ude{at}gmx.de)
  1. University of Erlangen, Germany
    1. Danielle Diarra (diarra{at}gmx.de)
    1. Medical University of Vienna, Austria
      1. Julia Katzenbeisser (katze{at}gmx.de)
      1. University of Erlangen, Germany
        1. Jean-Pierre David
        1. University of Erlangen, Germany
          1. Jochen Zwerina
          1. University of Erlangen, Germany
            1. William G Richards
            1. Amgen Inc, United States
              1. Gerhard Krönke (gerhard.kroenke{at}uk-erlangen.de)
              1. University of Erlangen, Germany
                1. Georg Schett (georg.schett{at}uk-erlangen.de)
                1. University of Erlangen, Germany

                  Abstract

                  Objective: To study whether Dickkopf (DKK)- 1, an inhibitor of Wnt signaling, is involved in the fusion of sacroiliac joints.

                  Methods: Mice transgenic for tumor necrosis factor (TNFtg mice), which develop bilateral sacroiliitis, were treated by vehicle, anti- TNF antibody or anti- DKK1 antibody. Sacroiliac joints were analyzed for histological signs of inflammation, bone erosion, osteoclast formation and ankylosis. Moreover, expression of collagen type X, β-catenin and DKK-1 was assessed by immunohistochemistry.

                  Results: There were no signs of spontaneous ankylosis of the sacroiliac joints in TNFtg mice. TNF blockade effectively reduced inflammation, bone erosion and osteoclasts numbers in the sacroiliac joints, but did not lead to ankylosis. Blockade of DKK1 has no effect on inflammatory signs of sacroiliitis, but significantly reduced bone erosions and osteoclast counts. Moreover, DKK1 blockade promoted expression of collagen type X, the formation of hypertrophic chondrocytes and ankylosis of sacroiliac joints.

                  Conclusion: DKK1 influences inflammatory remodeling of sacroiliac joints by prevention of joint ankylosis. This may indicate an important role of the Wnt signaling pathway in the structural bone changes of axial joint disease. Although this model does not reflect the entire spectrum of ankylosing spondylitis of humans, it helps to explain the pathophysiological processes of sacroiliac joint ankylosis, which is a hallmark of spondyloarthritides.

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