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Extended report
Blockade of Dickkopf (DKK)-1 induces fusion of sacroiliac joints
  1. S Uderhardt1,
  2. D Diarra2,
  3. J Katzenbeisser1,
  4. J-P David1,
  5. J Zwerina1,
  6. W Richards3,
  7. G Kronke1,
  8. G Schett1
  1. 1Department of Internal Medicine 3 and Institute for Clinical Immunology, University of Erlangen-Nuremberg, Erlangen, Germany
  2. 2Division of Rheumatology, Department of Internal Medicine III, Medical University of Vienna, Austria
  3. 3Amgen, Thousand Oaks, California, USA
  1. Correspondence to G Schett, Department of Internal Medicine III and Institute for Clinical Immunology, University of Erlangen-Nuremberg, Krankenhausstrasse 12, D-91054 Erlangen, Germany. EM; georg.schett{at}uk-erlangen.

Abstract

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

Methods Mice transgenic for tumour necrosis factor (TNFtg mice), which develop bilateral sacroiliitis, were treated with vehicle, anti-TNF antibody or anti-DKK1 antibody. Sacroiliac joints were analysed 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 osteoclast numbers in the sacroiliac joints, but did not lead to ankylosis. Blockade of DKK1 had 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 remodelling of sacroiliac joints by prevention of joint ankylosis. This may indicate an important role of the Wnt signalling pathway in the structural bone changes of axial joint disease. Although this model does not reflect the entire spectrum of ankylosing spondylitis in humans, it helps to explain the pathophysiological processes of sacroiliac joint ankylosis, which is a hallmark of the spondyloarthritides.

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Footnotes

  • de SU and DD contributed equally to this work.

  • Funding This study was funded by the START prize of the Austrian Science Fund (to GS), the Kompetenznetz Rheumatologie of the German Society of Rheumatology, the Interdisciplinary Centre for Clinical Research at the University of Erlangen (IZKF projects C6, IZKF project C7) and the SPIRAL consortium.

  • Competing interests None declared.

  • Ethics approval The local ethical committee approved all animal procedures.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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