关节炎发生的新机制—Wnt-β-catenin通过FOXP3参与调控调节性T细胞

There is a high incidence of arthritis in the older pepple with poor clinical outcome. It has a serious influence on patients' quality of life. Wnt/β -catenin signaling pathway plays an important role in the embryonic period of bone, cartilage formation and differentiation, and in the pathogenesis of arthritis. Regulatory T cells play an important role in the process of osteoarthritis and rheumatoid arthritis. Our preliminary study showed: Both of β -catenin and FoxP3 expression was significantly increased in mouse of osteoarthritis and rheumatoid arthritis model with a positive correlation. The high expression of Foxp3 is an important marker for Treg cells formation, and is a key transcription factor of Treg cells development and play a biological effect. Therefore, we propose the following hypothesis: Wnt/β-catenin signaling pathways regulate regulatory T cells through Foxp3 in inflammation process of osteoarthritis and rheumatoid arthritis. We will employ arthritis model, cell culture, molecular biological methods to prove the hypothesis and discovery new targets of therapeutic arthritis, and provide a new strategy for the treatment of osteoarthritis and rheumatoid arthritis.

关节炎在中老年人中发病率较高，但治疗效果欠佳，严重者影响患者生活质量。Wnt/β-catenin信号通路在胚胎期对骨、软骨的形成和分化及关节炎的发病过程中起着重要作用。调节性T（Treg）细胞在骨关节炎及类风湿关节炎中发挥重要的免疫调控作用。我们前期初步研究发现：β-catenin和Foxp3在小鼠骨关节炎及类风湿关节炎模型中表达显著升高，并呈正相关。Foxp3高表达是Treg细胞形成的重要标志，是影响Treg发育和发挥生物效应的关键转录因子。因此，我们提出如下假设：骨关节炎及类风湿关节炎中Wnt/β-catenin信号通路通过Foxp3，调控Treg细胞参与关节炎的炎症免疫过程。我们将综合运用关节炎模型、细胞培养、分子生物等方法，系统研究关节炎中Wnt/β-catenin信号通路对Foxp3的分子调控机制，发现新的关节炎治疗靶点，为骨关节炎及类风湿关节炎的治疗提供新策略。

Wnt/β-catenin 信号通路在胚胎期对骨、软骨的形成和分化及关节炎的发病过程中起着重要作用。调节性 T（Treg）细胞在骨关节炎及类风湿关节炎中发挥重要的免疫调控作用。研究发现：β-catenin 和 Foxp3 在小鼠骨关节炎及类风湿关节炎模型中表达显著升高，并呈正相关。Foxp3 高表达是 Treg 细胞形成的重要标志，是影响 Treg 发育和发挥生物效应的关键转录因子。本项目发现骨关节炎及类风湿关节炎中 Wnt/β-catenin信号通路通过 Foxp3，调控 Treg 细胞参与关节炎的炎症免疫过程。除此之外本项目还发现了和关节炎发生发展有密切关系的分子和调控基因如serpinE2，骨保护素Osteoprotegerin (OPG)，骨桥蛋白Osteopontin (OPN)，成纤维细胞生长因子23（FGF23），骨钙蛋白Osteocalcin (OC)，Leptin，VEGF，Fractalkine(CX3CL1) ，为骨关节炎及类风湿关节炎的治疗提供新的潜在的治疗靶点和新的防治策略。