巢乱蛋白2在类风湿关节炎软骨中的表达及其对软骨破坏的影响  

Expression of dishevelled-2 in cartilage of rheumatoid arthritis and its effect on cartilage destruction

作　　者：刘兴振 高颖 綦柯 赵东宝 Liu Xingzhen;Gao Ying;Qi Ke;Zhao Dongbao(Department of Rheumatology,Changhai Hospital,Naval Military Medical University,Shanghai 200433,China)

机构地区：[1]海军军医大学附属长海医院风湿免疫科,上海200433 [2]海军军医大学附属长海医院关节外科,上海200433

出　　处：《中华内科杂志》2018年第9期674-678,共5页Chinese Journal of Internal Medicine

基　　金：国家自然科学基金（81471607、81671595、81273284）

摘　　要：目的 探讨巢乱蛋白2 （DVL2）在类风湿关节炎（RA）膝关节软骨中的表达及其对软骨破坏的影响.方法 Western blot检测类风湿关节炎（RA）和骨关节炎（OA）患者及胶原诱导关节炎（CIA）大鼠和健康大鼠膝关节软骨中DVL2蛋白表达.将DVL2过表达慢病毒转染入CIA大鼠膝关节后,观察其对CIA大鼠关节软骨的影响;将DVL2过表达慢病毒转染入RA患者膝关节软骨细胞后,实时定量-聚合酶链式反应（RT-PCR）检测软骨细胞中细胞因子基因的表达.结果 RA患者膝关节软骨组织中DVL2蛋白表达高于OA患者（2.04±0.76比0.97±0.37,t=2.815,P=0.044）.CIA大鼠膝关节软骨中DVL2蛋白表达高于健康大鼠（2.18±0.68比0.92±0.05,t=2.921,P=0.042）.转染DVL2过表达慢病毒后对CIA大鼠膝关节软骨的破坏无显著影响（P=0.885）.转染DVL2过表达慢病毒后,可上调RA患者膝关节软骨细胞中环氧合酶2（COX-2）、诱导型一氧化氮合酶（iNOS）、基质金属蛋白酶（MMP）-2、MMP-3、MMP-9mRNA表达,当加入肿瘤坏死因子α（TNFα）刺激后,COX-2、iNOS、MMP-2、MMP-3、MMP-9mRNA表达更为明显.结论 DVL2在RA患者关节软骨中处于高表达,并通过激活Wnt/β-catenin通路促进软骨细胞破坏相关基因表达,从而参与RA关节软骨的破坏.Objective To study the expression of dishevelled-2 （DVL2） in rheumatoid arthritis cartilage and its effect on cartilage destruction.Methods Cartilage DVL2 expression in rat models of rheumatoid arthritis （RA）,osteoarthritis（OA） and collagen-induced arthritis（CIA） were tested by Western blotting.DVL2 overexpressed lentivirus was transfected into the knee of CIA rats.Primary chondrocytes were extracted from RA patients by knee arthroplasty and transfected with DVL2 overexpressed lentivirus.Gene expression of related inflammation related cytokines was detected by real-time polymerase chain reaction （PCR）.Results Compared with knee articular cartilage in OA patients and normal rats,DVL2 protein was highly expressed in knee cartilage of RA patients and CIA rats （P values 0.041 and 0.032,respectively）.DVL2 did not significantly affect the destruction of knee cartilage in CIA rats （P=0.885）.DVL2 overexpression in chondrocytes enhanced gene expression of cyclo-oxygenase-2 （COX-2）,inducible nitric oxide synthase （NOS）,matrix metalloproteinase （MMP） 2,MMP-3,and MMP-9,which could be more pronounced when tumor necrosis factor alpha was added.Conclusions DVL2 is highly expressed in RA articular cartilage and promotes the expression of inflammatory cytokines and MMP gene in chondrocytes by activating Wnt/β-catenin pathway,which involves in the destruction of articular cartilage in RA.

关 键 词：关节炎 类风湿 巢乱蛋白2 WNT信号通路 软骨细胞 

分 类 号：R593.22[医药卫生—内科学]