Schett Georg, Zwerina Jochen, David Jean-Pierre
Department of Internal Medicine 3, University of Erlangen-Nuremberg, Erlangen, Germany.
Nat Clin Pract Rheumatol. 2008 Sep;4(9):473-80. doi: 10.1038/ncprheum0881.
Wnt proteins regulate organ development, tumorigenesis and bone homeostasis, among other functions. The binding of Wnt proteins to plasma membrane receptors on mesenchymal cells induces the differentiation of these cells into the osteoblast lineage and thereby supports bone formation. Wnts are also key signaling proteins in joint remodeling processes. Active Wnt signaling contributes to osteophyte formation and might have an essential role in the anabolic pattern of joint remodeling that is observed in ankylosing spondylitis and osteoarthritis. By contrast, blockade of Wnt signaling facilitates bone erosion and contributes to catabolic joint remodeling, a process that is observed in rheumatoid arthritis. This Review summarizes current knowledge of the molecular regulation of joint remodeling associated with chronic arthritis, focusing on the role of the Wnt proteins and their inhibitors. It also addresses the role of Wnt in determining the differences in clinical presentation of inflammatory arthropathies and discusses implications for future therapy.
Wnt蛋白具有多种功能，包括调节器官发育、肿瘤发生和骨稳态等。Wnt蛋白与间充质细胞膜受体的结合可诱导这些细胞分化为成骨细胞谱系，从而支持骨形成。Wnt蛋白也是关节重塑过程中的关键信号蛋白。活跃的Wnt信号传导有助于骨赘形成，并且可能在强直性脊柱炎和骨关节炎中观察到的关节重塑合成代谢模式中起重要作用。相比之下，Wnt信号传导的阻断会促进骨侵蚀，并导致分解代谢性关节重塑，这一过程在类风湿性关节炎中可见。本综述总结了与慢性关节炎相关的关节重塑分子调控的当前知识，重点关注Wnt蛋白及其抑制剂的作用。它还探讨了Wnt在确定炎症性关节病临床表现差异方面的作用，并讨论了对未来治疗的影响。
