Laboratory of Tissue Homeostasis and Disease, Skeletal Biology and Engineering Research Center, Department of Development and Regeneration, KU Leuven, Herestraat 49, B3000 Leuven, Belgium.
Nat Rev Rheumatol. 2013 Jun;9(6):328-39. doi: 10.1038/nrrheum.2013.25. Epub 2013 Mar 5.
The Wnt signalling cascades have essential roles in development, growth and homeostasis of joints and the skeleton. Progress in basic research, particularly relating to our understanding of intracellular signalling cascades and fine regulation of receptor activation in the extracellular space, has provided novel insights into the roles of Wnt signalling in chronic arthritis. Cartilage and bone homeostasis require finely tuned Wnt signalling; both activation and suppression of the Wnt-β-catenin cascade can lead to osteoarthritis in rodent models. Genetic associations with the Wnt antagonist encoded by FRZB and the transcriptional regulator encoded by Dot1l with osteoarthritis further corroborate the essential part played by Wnts in the joint. In rheumatoid arthritis, inhibition of Wnt signalling has a role in the persistence of bone erosions, whereas Wnts have been associated with the ankylosing phenotype in spondyloarthritis. Together, these observations identify the Wnt pathway as an attractive target for therapeutic intervention; however, the complexity of the Wnt signalling cascades and the potential secondary effects of drug interventions targeting them highlight the need for further research and suggest that our understanding of this exciting pathway is still in its infancy.
Wnt 信号级联在关节和骨骼的发育、生长和稳态中起着至关重要的作用。基础研究的进展，特别是与我们对细胞内信号级联和细胞外空间受体激活的精细调节的理解有关，为 Wnt 信号在慢性关节炎中的作用提供了新的见解。软骨和骨骼的稳态需要精细调节的 Wnt 信号；Wnt-β-连环蛋白级联的激活和抑制都可能导致啮齿动物模型中的骨关节炎。与 FRZB 编码的 Wnt 拮抗剂和 Dot1l 编码的转录调节剂的遗传关联进一步证实了 Wnts 在关节中的重要作用。在类风湿关节炎中，抑制 Wnt 信号在骨侵蚀的持续存在中起作用，而 Wnts 与脊柱关节炎中的强直性表型有关。总之，这些观察结果将 Wnt 途径确定为治疗干预的一个有吸引力的靶点；然而，Wnt 信号级联的复杂性以及针对它们的药物干预的潜在次要效应突出表明需要进一步研究，并表明我们对这一令人兴奋的途径的理解仍处于起步阶段。
