兰克尔
炎症
医学
类风湿性关节炎
发病机制
滑膜炎
关节炎
白细胞介素
癌症研究
免疫学
内科学
受体
细胞因子
激活剂(遗传学)
作者
Lin Yuan,Yuxuan Li,Dan Liu,Hui Zhang,Jie Yang,Hui Shen,Liping Xia,Lutian Yao,Jing Lu
摘要
Abstract Rheumatoid arthritis (RA) is a chronic autoimmune disease. Its pathological features include synovial inflammation, bone erosion, and joint structural damage. Our previous studies have shown that interleukin (IL)‐35 is involved in the pathogenesis of bone loss in RA patients. In this study, we are further evaluating the efficacy of IL‐35 on collagen‐induced arthritis (CIA) in the mouse model. Male DBA/1J mice ( n = 10) were initially immunized, 2 μg/mouse IL‐35 was injected intraperitoneally every week for 3 weeks after the establishment of the CIA model. Clinical arthritis, histopathological analysis, and three‐dimensional micro‑computed tomography (3D micro‑CT) were determined after the mice were anesthetized on the 42th day. In vitro, RANKL/M‐CSF induced mouse preosteoclasts (RAW264.7 cells line) was subjected to antiarthritis mechanism study in the presence of IL‐35. The results of clinical arthritis, histopathological analysis, and 3D micro‑CT, the expression of RANK/RANKL/OPG axis, inflammatory cytokines, and osteoclastogenesis‐related makers demonstrated decreasing severity of synovitis and bone destruction in the ankle joints after IL‐35 treatment. Furthermore, IL‐35 attenuated inflammatory cytokine production and the expression of osteoclastogenesis‐related makers in a mouse preosteoclasts cell line RAW264.7. The osteoclastogenesis‐related makers were significantly reduced in IL‐35 treated RAW264.7 cells line after blockage with the JAK/STAT1 signaling pathway. These results demonstrated that IL‐35 protein could inhibits osteoclastogenesis and attenuates CIA in mice. We concluded that IL‐35 can exhibit anti‐osteoclastogenesis effects by reducing the expression of inflammatory cytokines and osteoclastogenesis‐related makers, thus alleviating bone destruction in the ankle joint and could be a potential therapeutic target for RA.
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