Department of Orthopaedic Surgery and Muscloskeletal Science, Graduate School of Medicine, Yokohama City University, Yokohama, Japan.
Department of Molecular Pathology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
J Orthop Res. 2024 Aug;42(8):1880-1889. doi: 10.1002/jor.25825. Epub 2024 Mar 5.
The aim of the present study was to investigate the association between chondrogenic differentiation and Wnt signal expression in the degenerative process of the human meniscus. Menisci were obtained from patients with and without knee osteoarthritis (OA), and degeneration was histologically assessed using a grading system. Immunohistochemistry, real-time polymerase chain reaction (PCR), and Western blot analysis were performed to examine the expressions of chondrogenic markers and of the components of Wnt signaling. Histological analyses showed that meniscal degeneration involved a transition from a fibroblastic to a chondrogenic phenotype with the upregulation of SOX9, collagen type II, collagen type XI, and aggrecan, which were associated with increased Wnt5a and ROR2 and decreased TCF7 expressions. OA menisci showed significantly higher expressions of Wnt5a and ROR2 and significantly lower expressions of AXIN2 and TCF7 than non-OA menisci on real-time PCR and Western blot analysis. These results potentially demonstrated that increased expression of Wnt5a/ROR2 signaling promoted chondrogenesis with decreased expression in downstream Wnt/β-catenin signaling. This study provides insights into the role of Wnt signaling in the process of meniscal degeneration, shifting to a chondrogenic phenotype. The findings suggested that the increased expression of Wnt5a/ROR2 and decreased expression of the downstream target of Wnt/β-catenin signaling are associated with chondrogenesis in meniscal degeneration.
本研究旨在探讨软骨分化与 Wnt 信号在人类半月板退行性过程中的关系。从膝骨关节炎（OA）患者和非 OA 患者中获取半月板，并使用分级系统进行组织学评估。通过免疫组织化学、实时聚合酶链反应（PCR）和 Western blot 分析，检测软骨生成标志物和 Wnt 信号成分的表达。组织学分析表明，半月板退变涉及从成纤维细胞向软骨细胞表型的转变，伴随着 SOX9、胶原 II 型、胶原 XI 型和聚集蛋白聚糖的上调，这与 Wnt5a 和 ROR2 的增加以及 TCF7 表达的减少有关。实时 PCR 和 Western blot 分析显示，OA 半月板中 Wnt5a 和 ROR2 的表达明显高于非 OA 半月板，AXIN2 和 TCF7 的表达明显低于非 OA 半月板。这些结果可能表明，Wnt5a/ROR2 信号的表达增加促进了软骨生成，而下游 Wnt/β-连环蛋白信号的表达减少。本研究深入了解了 Wnt 信号在半月板退变过程中的作用，向软骨细胞表型转变。研究结果表明，Wnt5a/ROR2 的表达增加和 Wnt/β-连环蛋白信号下游靶标表达的减少与半月板退变中的软骨生成有关。
