Abstract：
Rheumatoid arthritis (RA) is a chronic immune disease involving the small joints, which often causes irreversible damage. In recent years, elevated interleukin 20 (IL-20) has been observed in synovial fluid, while IL-20 receptor overexpression has been observed in synovial cells. IL-20 is a pleiotropic cytokine that participates in various immune diseases. Further understanding of the relationship between IL-20 and RA can help to identify a potential clinical treatment for RA. This study demonstrated that IL-20 can regulate osteoclast differentiation and function in a dose-dependent manner, while influencing the expression of Notch signalling. Quantitative reverse transcription polymerase chain reaction and western blotting showed that γ-secretase-inhibiting drugs can reverse the effects of IL-20. The effects of Notch2 on IL-20-induced osteoclastogenesis were investigated by immunofluorescence and Notch2 gene silencing via transfection of small interfering RNA; the results showed that Notch2 obviously affected the expression levels of the key protein NFATc1 and downstream osteoclastic proteins. In conclusion, we found that IL-20 regulated the osteoclastogenesis in a dose-dependent manner via Notch signalling, primarily by means of Notch2 activity. This study may help to find new targets for RA treatment.
摘要：
类风湿性关节炎(RA)是一种累及小关节的慢性免疫性疾病,这往往会造成不可逆转的损害。近年来,在滑液中观察到白细胞介素20（IL-20）升高，而在滑膜细胞中观察到IL-20受体过表达。IL-20是一种多效性细胞因子，参与各种免疫疾病。进一步了解IL-20与RA之间的关系有助于确定RA的潜在临床治疗方法。这项研究表明，IL-20可以剂量依赖的方式调节破骨细胞的分化和功能，同时影响Notch信号的表达。定量逆转录聚合酶链反应和免疫印迹表明γ-分泌酶抑制药物可以逆转IL-20的作用。通过免疫荧光和转染小干扰RNA沉默Notch2基因，研究了Notch2对IL-20诱导的破骨细胞生成的影响；结果表明，Notch2明显影响关键蛋白NFATc1和下游破骨细胞蛋白的表达水平。总之,我们发现IL-20通过Notch信号以剂量依赖的方式调节破骨细胞的生成,主要通过Notch2活性。本研究可能有助于寻找RA治疗的新靶点。
