Objective: To summarize the active changes of Wnt signaling pathway in osteoarthritis (OA) as well as the influence and mechanism of dual-targeted regulation on cartilage and subchondral bone and the role of crosstalk between them on OA process.
Methods: The relevant literature concerning the articular cartilage, subchondral bone, and crosstalk between them in OA and non-OA states by Wnt signaling pathway in vivo and vitro experimental studies and clinical studies in recent years was reviewed, and the mechanism was analyzed and summarized.
Results: Wnt signaling can regulate the differentiation and function of chondrocytes and osteoblasts through the classic β-catenin-dependent or non-classical β-catenin-independent Wnt signaling pathway and its cross-linking with other signaling pathways, thereby affecting the cartilage and bone metabolism. Moreover, Wnt signaling pathway can activate the downstream protein Wnt1-inducible-signaling pathway protein 1 to regulate the progress of OA and it also can be established gap junctions between different cells in cartilage and subchondral bone to communicate molecules directly to regulate OA occurrence and development. Intra-articular injection of Wnt signaling inhibitor SM04690 can inhibit the progress of OA, and overexpression of Wnt signaling pathway inhibitor Dickkopf in osteoblasts can antagonize the role of vascular endothelial growth factor work on chondrocytes and inhibit the catabolism of its matrix.
Conclusion: The regulation of metabolism and function of cartilage and subchondral bone and crosstalk between them is through interactions among Wnt signaling pathway and molecules of other signaling. Therefore, it plays an vital role in the occurrence and development of OA and is expected to become a new target of OA treatment through intervention and regulation of Wnt signaling pathway.
目的: 综述 Wnt 信号通路在骨关节炎（osteoarthritis，OA）发生发展中的活性变化，及其对软骨、软骨下骨的双靶向调控和两者间信息交流对 OA 进程的影响和机制。.
方法: 查阅近年在体内外实验研究及临床研究中，OA 和非 OA 状态下 Wnt 信号通路对关节软骨、软骨下骨调控作用及软骨与软骨下骨间信息交流的相关文献，并对其作用机制进行分析总结。.
结果: Wnt 信号可通过依赖 β-catenin 的经典或不依赖 β-catenin 的非经典 Wnt 信号通路及其与其他信号通路的交联，调控软骨细胞、成骨细胞的分化和功能，进而影响软骨及骨的代谢。过度激活 Wnt 信号可加重软骨 OA 样退变，并且 Wnt 信号通路可激活下游蛋白 Wnt1 诱导的信号通路蛋白 1 调控 OA 进展，还可通过软骨及软骨下骨中不同细胞间建立的缝隙连接，直接进行分子交流调控 OA 的发生发展。关节腔内注射 Wnt 信号通路抑制剂 SM04690 可以抑制 OA 进程；在成骨细胞中过表达 Wnt 信号通路抑制剂 Dickkopf 可以拮抗 VEGF 对软骨细胞的作用，并抑制其基质的分解代谢。.
结论: Wnt 信号通路及其与其他信号分子的交互作用，可调控软骨和软骨下骨的代谢和功能及两者间信息交流，因此在 OA 的发生发展中发挥重要作用，有望成为 OA 治疗的新靶点。.
Keywords: Osteoarthritis; Wnt signaling pathway; articular cartilage; subchondral bone; β-catenin.