Department of Internal Medicine 3 and Institute for Clinical Immunology, University of Erlangen-Nuremberg, Erlangen, Germany.
Ann Rheum Dis. 2010 Mar;69(3):592-7. doi: 10.1136/ard.2008.102046. Epub 2009 Mar 19.
To study whether Dickkopf (DKK)-1, an inhibitor of wingless (Wnt) signalling, is involved in the fusion of sacroiliac joints.
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.
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.
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.
研究 Wnt 信号通路抑制剂 Dickkopf-1（DKK-1）是否参与骶髂关节融合。
使用肿瘤坏死因子（TNF）转基因（TNFtg 小鼠），双侧骶髂关节炎模型，用 vehicle（载体）、抗 TNF 抗体或抗 DKK1 抗体进行处理。分析骶髂关节的炎症、骨侵蚀、破骨细胞形成和融合的组织学表现。此外，通过免疫组化评估胶原蛋白 X、β-连环蛋白和 DKK-1 的表达。
TNFtg 小鼠的骶髂关节没有自发融合的迹象。TNF 阻断有效地减少了骶髂关节的炎症、骨侵蚀和破骨细胞数量，但不会导致融合。DKK1 阻断对骶髂关节炎的炎症迹象没有影响，但明显减少了骨侵蚀和破骨细胞数量。此外，DKK1 阻断促进了胶原蛋白 X 的表达、肥大软骨细胞的形成和骶髂关节的融合。
DKK1 通过防止关节融合来影响骶髂关节的炎症重塑。这可能表明 Wnt 信号通路在轴性关节疾病的结构骨变化中具有重要作用。虽然该模型不能反映人类强直性脊柱炎的全部特征，但它有助于解释骶髂关节融合的病理生理过程，这是脊柱关节炎的一个标志。
