Laboratory for Tissue Homeostasis and Disease, Skeletal Biology and Engineering Research Centre, Department of Development and Regeneration, Katholieke Universiteit Leuven, Herestraat 49, B-3000 Leuven, Belgium.
Division of Rheumatology, University Hospitals Leuven, Herestraat 49, B-3000 Leuven, Belgium.
Nat Rev Rheumatol. 2017 Nov;13(11):670-681. doi: 10.1038/nrrheum.2017.171. Epub 2017 Oct 12.
Wnt signalling pathways have key roles in joint development, homeostasis and disease, particularly in osteoarthritis. New data is starting to reveal the importance of tightly regulating canonical Wnt signalling pathway activation to maintain homeostasis and health in articular cartilage. In addition to the presence of different Wnt antagonists that limit pathway activation in articular cartilage, the reciprocal crosstalk between the canonical and non-canonical cascades and competitive antagonism between different Wnt ligands seem to be critical in restraining excessive Wnt pathway activation. Changes in transcriptional complex assembly upon Wnt pathway activation, epigenetic modulation of target gene transcription, in particular through histone modifications, and complex interactions between the Wnt signalling pathway and other signalling pathways, are also instrumental in adjusting Wnt signalling. In this Review, the cellular and molecular mechanisms involved in fine-tuning canonical Wnt signalling in the joint are updated, with a focus on the articular cartilage. The interventions for preventing or treating osteoarthritis are also discussed, which should aim to limit disease-associated excessive canonical Wnt activity to avoid joint damage.
Wnt 信号通路在关节发育、稳态和疾病中（尤其是在骨关节炎中）发挥着关键作用。新的数据开始揭示出，在关节软骨中，严格调控经典 Wnt 信号通路的激活对于维持其稳态和健康非常重要。除了存在不同的 Wnt 拮抗剂来限制关节软骨中通路的激活外，经典和非经典级联之间的相互串扰以及不同 Wnt 配体之间的竞争拮抗作用，似乎对于抑制过度的 Wnt 通路激活至关重要。Wnt 通路激活时转录复合物组装的变化、靶基因转录的表观遗传调控，特别是通过组蛋白修饰，以及 Wnt 信号通路与其他信号通路之间的复杂相互作用，也有助于调节 Wnt 信号。在这篇综述中，更新了参与调节关节中经典 Wnt 信号的细胞和分子机制，重点关注关节软骨。还讨论了预防或治疗骨关节炎的干预措施，这些措施应该旨在限制与疾病相关的经典 Wnt 过度活性，以避免关节损伤。
