干扰素β通过RANK/RANKL信号分子调控胶原抗体诱导关节炎小鼠的分子学机制  

Molecular mechanism of IFN-beta interference via RANK/RANKL signaling in CAIA mice model

作　　者：陈呢喃[1] 赵蓉[1] 周晓薇[1] 苗平[1] 许荣 张冬青[1] 

机构地区：[1]上海交通大学医学院上海市免疫学研究所,上海200025 [2]上海长宁区光华中西结合医院中心实验室,上海200052

出　　处：《诊断学理论与实践》2014年第1期61-67,共7页Journal of Diagnostics Concepts & Practice

基　　金：国家自然科学基金(31270963);上海市科委重点项目(10JC1408500;09DZ2260200)

摘　　要：目的:研究干扰素β(interferonβ,IFN-β)在抗胶原Ⅱ功能域抗体诱导的小鼠类风湿性关节炎(rheumatoid arthritis,RA)样模型中的调控作用,探讨RA潜在的干预新靶点。方法:应用抗胶原Ⅱ功能域抗体诱导建立胶原抗体诱导关节炎(collagen antibody induced arthritis,CAIA)小鼠模型,通过其表型、关节评分、免疫组织化学染色、X射线衍射分析是否建模成功,并用IFN-β基因工程药物干预,RANK体外诱导破骨细胞生成,抗酒石酸酸性磷酸酶染色法检测破骨细胞数量,实时荧光定量聚合酶链反应检测RANK/RANKL关键分子变化。结果:CAIA小鼠建模成功,IFN-β能显著缓解CAIA小鼠的病情,实时荧光定量聚合酶链反应显示IFN-β干预后小鼠骨关节中c-FOS、NFATc-1的表达量下降,IFN-β能抑制破骨细胞生成。结论:IFN-β缓解CAIA小鼠模型发病的可能机制是通过RANK/RANKL-IFN-β-NFATc-1下调破骨细胞的生成。Objective： To investigate the effect of IFN-beta intervention on rheumatoid arthritis （RA）like collagen antibody induced arthritis （CAIA） mice model and to study the potential target for therapy. Methods： RA like mice model was induced by anti-collagen II functional domains antibody in BALB/c mice and was then interfered by IFN-beta. The genotype of mice, severity of arthritis （according to the standard evaluation of mice joints）,immunohistochemical stain- ing, and X-ray diffraction were used to judge the CAIA model mice. Degree of inflammatory cells infiltration and cartilage destraction were assessed by hematoxylin - eosin staining and safranin O staining, respectively. Osteoclast was induced in vitro by RANK, and was counted using tartrate resistant acid phosphatase. The changes of RANKL-RANK signaling mark- ers （such as RANK, TRAF6, c-Fos, NFATc-1） were detected by real time-PCR. Results： CAIA mice model was estab- lished successfully. After interfered with IFN-beta, the morbidity and arthritis score of the model mice were decreased sig- nificantly, real time-PCR showed that IFN-beta could down-regulate the expression of key molecules of RANK/RANKL pathway; IFN-beta could inhibit osteoclastogenesis. Conclusions： IFN-beta may down- osteoclastogenesis v/a RANK/ RANKL-IFN-15-NFATc-1 pathway and ameliorate RA symptoms of CAIA mice.

关 键 词：胶原抗体诱导关节炎 RANK RANKL信号通路 干扰素Β 破骨细胞 

分 类 号：R593.22[医药卫生—内科学]