Related Experiment Video
Updated: Jun 24, 2026
Studying Mitotic Checkpoint by Illustrating Dynamic Kinetochore Protein Behavior and Chromosome Motion in Living Drosophila Syncytial Embryos
Published on: June 14, 2012
Blockade of Dickkopf (DKK)-1 induces fusion of sacroiliac joints
S Uderhardt1, D Diarra, J Katzenbeisser
1Department of Internal Medicine 3 and Institute for Clinical Immunology, University of Erlangen-Nuremberg, Erlangen, Germany.
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, beta-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.
Insights
Dickkopf-1 (DKK-1) blockade prevents sacroiliac joint fusion in a mouse model of inflammatory arthritis. DKK-1 inhibition promotes ankylosis, suggesting a role in axial joint disease.
Area of Science:
- Immunology
- Rheumatology
- Molecular Biology
Background:
- Sacroiliac joint fusion is a hallmark of spondyloarthropathies.
- Wingless (Wnt) signaling plays a role in bone remodeling.
- Dickkopf-1 (DKK-1) is an inhibitor of Wnt signaling.
Purpose of the Study:
- To investigate the role of DKK-1 in sacroiliac joint fusion.
- To determine if DKK-1 inhibition affects inflammatory arthritis and joint ankylosis.
Main Methods:
- Utilized tumor necrosis factor transgenic (TNFtg) mice with bilateral sacroiliitis.
- Administered vehicle, anti-TNF antibody, or anti-DKK1 antibody.
- Analyzed sacroiliac joints for inflammation, bone erosion, osteoclast formation, and ankylosis via histology and immunohistochemistry.
Main Results:
- TNF blockade reduced inflammation, bone erosion, and osteoclast numbers but did not induce ankylosis.
- DKK1 blockade did not affect inflammation but significantly reduced bone erosions and osteoclast counts.
- DKK1 blockade promoted collagen type X expression, hypertrophic chondrocytes, and sacroiliac joint ankylosis.
Conclusions:
- DKK1 influences inflammatory sacroiliac joint remodeling by preventing joint ankylosis.
- The Wnt signaling pathway is implicated in structural bone changes in axial joint disease.
- This model elucidates pathophysiological processes of sacroiliac joint ankylosis in spondyloarthropathies.
Related Concept Videos
01:17Intracellular Signaling Affects Focal Adhesions
Some...
02:19The Spindle Assembly Checkpoint
Many proteins function together to control the spindle assembly checkpoint. Mutations affecting these proteins may allow cells to proceed into anaphase prematurely, resulting in the...