糖蛋白130相关炎症因子介导RA患者破骨细胞分化的初步研究

A preliminary study of gp130-related inflammatory factors regulating osteoclast differentiation in RA patients

目的:研究糖蛋白130(gp130)及其相关炎症因子在类风湿关节炎(RA)患者外周血中的表达及调控gp130对破骨细胞分化的影响。方法:研究组选取47例RA患者样本,对照组选取40例健康献血者,用酶联免疫法检测两组血清IL-6、IL-6Rα、gp130、IL-11、IL-27及MMP-9的表达,并通过抗人gp130 单克隆抗体(McAb)处理其外周血单个核细胞(PBMC)经诱导向破骨样细胞(OLC)分化的过程,同时检测OLC细胞表面gp130 表达水平以及TRAP阳性细胞数,IL-6、MMP-9及STAT3磷酸化的含量。结果:与对照组比:RA患者血清IL-6、IL-11、IL-27 含量及IL-6Rα/gp130比值显著升高(P<0.05),RA患者组PBMC经RANKL诱导后高表达gp130、IL-6和MMP-9,且TRAP阳性破骨细胞数明显增多(P<0.05)。用抗gp130 McAb处理RA患者的PBMC后,上述指标均有显著下降(P<0.05),同时,其STAT3磷酸化水平也受到不同程度的下调。结论:RA患者IL-6、IL-11、IL-27均通过其受体gp130参与了RA发病发展的进程。初步实验表明,gp130不仅高表达且是RA患者体内破骨细胞分化的关键因子,应用抗gp130 McAb调控gp130功能的异常表达为临床干预治疗RA提供了新的方法与手段。

Objective:To investigate the expression of gp130 and its correlated inflammatory factors in peripheral blood of patients with rheumatoid arthritis (RA) and the effect of gp130 on differentiation of osteoclast.Methods:47 samples of RA patients in the study group and 40 healthy blood donors in the control group were selected.The expression of serum IL-6,IL-6Ralpha,gp130,IL-11,IL-27 and MMP-9 of two groups were detected by ELISA.The differentiation of peripheral blood mononuclear cells (PBMC) into osteoclast-like cells (OLC) was induced by anti-human gp130 monoclonal antibody,and the expression of gp130 on the surface of OLC,the number of TRAP positive cells,the levels of IL-6 and MMP-9 and the phosphorylation of STAT3 were detected.Results:Compared with the control group,the serum levels of IL-6,IL-11,IL-27 and the ratio of IL-6Ralpha/gp130 in RA patients were significantly increased (P<0.05).The expression of gp130,IL-6 and MMP-9 in PBMC from RA patients was significantly increased after induction by RANKL,and the number of TRAP-positive osteoclasts was significantly increased (P<0.05).After treatment of PBMC from RA patients with anti-gp130 McAb,the above-mentioned indexes were significantly decreased (P<0.05).The phosphorylation level of STAT3 was also reduced in varying degrees.Conclusion:IL-6,IL-11 and IL-27 are all involved in the pathogenesis of RA through their receptors gp130.Preliminary experiments show that gp130 is not only overexpressed but also a key factor for osteoclast differentiation in RA patients.Using anti-gp130 McAb to regulate the abnormal expression of gp130 function may provide a new method and means for clinical intervention in the treatment of RA patients.