[1]戴冠东 徐勇 戴勇 叶小林 刘国辉△ 陈熹.脂联素对体外培养人类风湿关节炎滑膜 成纤维细胞合成MMP-3的影响[J].中国中医骨伤科杂志,2015,23(12):1-5.
 DAI Guandong XU Yong DAI Yong YE Xiaolin LIU Guohui CHEN Xi.Effect of Adiponectin on the Synthesis of MMP-3 in Human Synovial Fibroblasts of Rheumatoid Arthritis in Vitro[J].Chinese Journal of Traditional Medical Traumatology & Orthopedics,2015,23(12):1-5.
点击复制

脂联素对体外培养人类风湿关节炎滑膜 成纤维细胞合成MMP-3的影响
分享到:

《中国中医骨伤科杂志》[ISSN:1005-0205/CN:42-1340/R]

卷:
第23卷
期数:
2015年12期
页码:
1-5
栏目:
实验研究
出版日期:
2015-12-08

文章信息/Info

Title:
Effect of Adiponectin on the Synthesis of MMP-3 in Human Synovial Fibroblasts of Rheumatoid Arthritis in Vitro
文章编号:
1005-0205(2015)12-0001-05
作者:
戴冠东1 徐勇1 戴勇1 叶小林1 刘国辉2△ 陈熹2
1.广东省深圳市坪山新区人民医院骨一区(广东 深圳,518118)
2.华中科技大学同济医学院附属协和医院骨科
△.通信作者 E-mail:liuguohui@medmail.com.cn
Author(s):
DAI Guandong1 XU Yong1 DAI Yong1 YE Xiaolin1 LIU Guohui2△ CHEN Xi2
1.First Department of Orthopedics,People' Hospital of Pingshan District,Shenzhen 518118,Guangdong China;
2.Department of Orthopedics,Union Hospital Affiliated to Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430022,China.
关键词:
类风湿关节炎 脂联素 基质金属蛋白酶-3(MMP-3)
Keywords:
rheumatoid arthritis adiponectin MMP-3
分类号:
R-33
文献标志码:
A
摘要:
目的:探讨脂联素对类风湿关节炎(RA)滑膜成纤维细胞合成分泌MMP-3的影响机制。方法:购买培养类风湿关节炎滑膜成纤维细胞(MH7A),给予脂联素刺激,观察不同浓度及时间下MMP-3 mRNA及蛋白的合成分泌情况; 随后通过NF-κB抑制剂检测最常见的炎性通路NF-κB是否参与了本调控; 最后采用慢病毒基因沉默的手段,检测NF-κB通路的亚基p65和IKKβ的参与情况。结果:脂联素促进人滑膜成纤维细胞中MMP-3 mRNA和蛋白的表达,并呈时间、剂量依赖效应。脂联素是通过NF-κB通路参与调控人滑膜成纤维细胞中MMP-3的表达,NF-κB通路中p65和IKKβ介入了脂联素对MMP-3的调控。结论:脂联素通过NF-κB(p65,IKKβ)通路促进类风湿关节炎滑膜成纤维细胞MMP-3的表达,提示脂联素可能为RA的前炎性因子,参与了RA的发生发展。
Abstract:
Objective:To investigate the effect of adiponectin on the synthesis and secretion of MMP-3 in synovial fibroblasts of rheumatoid arthritis.Methods:The synovial fibroblasts(MH7A)of rheumatoid arthritis were stimulated by adiponectin.The synthesis and secretion of MMP-3 mRNA and protein were observed under different concentrations and time points.The NF-κB inhibitor was used to detect if the NF-κB,one of common inflammatory signal pathway,was involved the regulation.The slow virus gene silencing methods were used to detect the participation of p65 and IKKβ,the subunit of NF-κB.Results:Adiponectin promoted the expression of MMP-3 mRNA and protein in human synovial fibroblasts,and it was time and dose dependent effect.Adiponectin was involved in the regulation of MMP-3 expression in human synovial fibroblasts by NF-κB signal pathway,and the p65 and IKKB were involved too.Conclusion:Adiponectin can promote the expression of MMP-3 in synovial fibroblasts of rheumatoid arthritis by NF-κB signal pathway,which suggesting that adiponectin may be a proinflammatory factor and involved in the development of rheumatoid arthritis.

参考文献/References:

[1] Noss EH,Brenner MB.The role and therapeutic implications of fibroblast-like synoviocytes in inflammation and cartilage erosion in rheumatoid arthritis[J].Immunol Rev,2008,223:252-270.
[2] Jin LP,Fan DX,Li DJ.Regulation of costimulatory signal in maternal-fetal immune tolerance[J].Am J Reprod Immunol,2011,66(2):76-83.
[3] Tong KM,Chen CP,Huang KC,et al.Adiponectin increases MMP-3 expression in human chondrocytes through AdipoR1 signaling pathway[J].J Cell Biochem,2011,112(5):1431-1440.
[4] Suzuki M,Mihara M.Adiponectin induces CCL20 expression synergistically with IL-6 and TNF-alpha in THP-1 macrophages[J].Cytokine,2012,58(3):344-350.
[5] Kusunoki N,Kitahara K,Kojima F,et al.Adiponectin stimulates prostaglandin E(2)production in rheumatoid arthritis synovial fibroblasts[J].Arthritis Rheum,2010,62(6):1641-1649.
[6] Kitahara K,Kusunoki N,Kakiuchi T,et al.Adiponectin stimulates IL-8 production by rheumatoid synovial fibroblasts[J].Biochem Biophys Res Communications,2009,378(2):218-223.
[7] Tang CH,Chiu YC,Tan TW,et al.Adiponectin enhances IL-6 production in human synovial fibroblast via an AdipoR1 receptor,AMPK,p38,and NF-kappa B pathway[J].J Immunology,2007,179(8):5483-5492.
[8] Singh D,Srivastava SK,Chaudhuri TK,et al.Multifaceted role of matrix metalloproteinases(MMPs)[J].Front Mol Biosci,2015,2:19.
[9] Sugiyama E.Role of matrix metalloproteinase-3 in joint destruction in rheumatoid arthritis[J].Clin Calcium,2007,17(4):528-534.
[10] Momohara S,Yamanaka H.Immunological and serological tests for diagnosis of rheumatoid arthritis:MMP-3[J].Nihon Rinsho,2005,63(S1):313-317.
[11] Rossi D,Modena V,Sciascia S,et al.Rheumatoid arthritis:biological therapy other than anti-TNF[J].Int Immunopharmacology,2015,27(2):185-188.
[12] Shapiro L,Scherer PE.The crystal structure of a complement-1q family protein suggests an evolutionary link to tumor necrosis factor[J].Curr Biol,1998,8(6):335-338.
[13] Schaffler A,Ehling A,Neumann E,et al.Adipocytokines in synovial fluid[J].Jama,2003,290(13):1709-1710.
[14] Ehling A,Schaffler A,Herfarth H,et al.The potential of adiponectin in driving arthritis[J].J Immunol,2006,176(7):4468-4478.
[15] 陈辉,马超,张育先.脂联素通过P38MAPK通路条件大鼠肝形状细胞MMP-13及TIMP-1表达[J].首都医科大学学报,2010,31(3):304-306.
[16] Tordella L,Koch S,Salter V,et al.ASPP2 suppresses squamous cell carcinoma via RelA/p65-mediated repression of p63[J].Proc Nat Acad Sci(USA),2013,110(44):17969-17974.
[17] Ohashi K,Yuasa D,Shibata R,et al.Adiponectin as a target in obesity-related inflammatory state[J].Endocr Metab Immune Disord Drug Targets,2015,15(2):145-150.
[18] Amsen D,Antov A,Jankovic D,et al.Direct regulation of Gata3 expression determines the T helper differentiation potential of Notch[J].Immunity,2007,27(1):89-99.

备注/Memo

备注/Memo:
收稿日期:2015-06-03
基金项目:深圳市科技计划项目(201303257)
深圳市坪山新区医疗卫生孵化资助项目(201341)
更新日期/Last Update: 2015-12-15