期刊文献+

骨关节炎患者关节软骨TIMP-3启动子区甲基化水平的初步研究 被引量:3

Investigation of TIMP-3 gene promoter methylation level in joint cartilage of osteoarthriti patients
下载PDF
导出
摘要 目的探讨关节软骨中组织金属蛋白酶抑制因子-3(TIMP-3)基因启动子区甲基化与其蛋白表达的相关性,并分析TIMP-3基因CpG岛异常甲基化与骨关节炎(OA)的关联性。方法应用甲基化特异性的聚合酶链反应(MSP)技术和免疫组织化学SP法分别检测14例健康人的正常关节软骨细胞和35例骨关节炎(OA)患者软骨细胞TIMP-3基因启动子区甲基化和蛋白表达情况。结果 OA患者和健康人关节软骨中TIMP-3基因启动子区均有甲基化修饰,其阳性率分别为74.3%(26/35)和35.7%(5/14),OA组TIMP-3基因启动子区甲基化率明显高于健康组(P<0.05)。14例健康人中,软骨细胞TIMP-3蛋白表达阳性10例(71.4%),而35例OA患者中,软骨细胞TIMP-3蛋白表达阳性11例(31.4%)。24例OA患者软骨细胞蛋白表达阴性的标本中,TIMP-3启动子区甲基化阳性21例(87.5%);26例TIMP-3启动子区甲基化阳性的标本中,蛋白表达阴性21例(80.8%),TIMP-3启动子区甲基化与蛋白表达呈显著负相关(P<0.05)。结论启动子区CpG岛高甲基化是OA患者关节软骨细胞TIMP-3表达失活的主要机制之一,其可能参与了OA的发生和发展。 Objective To investigate the relationship between the methylation of tissue inhibitor of metalloproteinase-3 (TIMP-3) gene promoter and its protein expression, to study the potential role of hyper-methylation of TIMP-3 gene in the development of osteoarthritis. Methods The CpG islands methylation levels of TIMP-3 promoter in joint cartilage cells were studied by methylation-specific PCR(MSP). TIMP-3 protein expression in joint cartilage cells were detected by immunohistochemical method in 35 osteoarthritis (OA) patients and 14 control health people. Results The positive percent of TIMP-3 promoter methylation levels in healthy people and OA patients were 35.7%(5/14) and 74.3%(26/35) respectively. The positive percent of TIMP-3 protein expression in OA patients were higher than healthy people (P〈 0.05); In cartilage cells, the positive percent of TIMP-3 protein expression in healthy people and OA patients were 71.4%(10/14) and 31.4%(11/35) respectively. In 24 cases of OA samples with negative cartilage cells protein expres- sion, 21 cases (87.5%)was found with positive TIMP-3 promoter methylation, and in 26 cases of patients with positive TIMP-3 promoter methylation, protein expression was negative in 21 cases (80.8%);Promoter methylation and TIMP-3 protein expression level showed significantly negative correlation. Conclusion TIMP-3 promoter is hyper-methlated in joint cartilage cells of OA patients. The hyper-methylation affects the protein expression of TIMP-3, which may play a crtical role in the occurrence and development of OA.
出处 《中国当代医药》 2014年第2期4-7,共4页 China Modern Medicine
基金 湖南省科技计划一般项目(2010FJ6004)
关键词 骨关节炎 甲基化 TIMP-3启动子 CPG岛 Osteoarthritis Methylation Tissue inhibitor of metalloproteinase-3 gene promoter CpG islands
  • 相关文献

参考文献12

  • 1Spector TD,MacGregor AJ. Risk factors for osteoarthritis:genetics[J].{H}Osteoarthritis and cartilage,2004,(Suppl A):39-44.
  • 2Roach HI,Yamada N,Cheung KS. Association between the abnormal expression of matrix-degrading enzymes by human osteoarthritic chondrocytes and demethylation of specific CpG sites in the promoter regions[J].{H}ARTHRITIS AND RHEUMATISM,2005,(10):3110-3124.
  • 3Kashiwagi M,Tortorella M,Nagase H. TIMP-3 is a potent inhibitor of aggrecanase 1 (ADAM-TS4)and aggrecanase 2 (ADAM-TS5)[J].{H}Journal of Biological Chemistry,2001,(16):12501-12504.
  • 4Smookler DS,Mohammed FF,Kassiri Z. Tissue inhibitor of metalloproteinase 3 regulates TNF-dependent systemic inflammation[J].{H}Journal of Immunology,2006,(2):721-725.
  • 5Mahmoodi M,Sahebjam S,Smookler D. Lack of tissue inhibitor of metalloproteinases-3 results in an enhanced inflammatory response in antigen-induced arthritis[J].Am J Patho1,2005,(6):1733-1740.
  • 6Arden N,Nevitt MC. Osteoarthritis:epidemiology[J].{H}BEST PRACTICE & RESEARCH IN CLINICAL RHEUMATOLOGY,2006,(1):3-25.
  • 7Hashimoto G,Aoki T,Nakamura H. Inhibition of ADAMTS4 (aggrecanase-1)by tissue inhibitors of metalloproteinases (TIMP-1,2,3 and 4)[J].{H}FEBS Letters,2001,(3):192-195.
  • 8Kevorkian L,Young DA,Darrah C. Expression profiling of metalloproteinases and their inhibitors in cartilage[J].{H}ARTHRITIS AND RHEUMATISM,2004,(1):131-141.
  • 9Zeng Y,Rosborough RC,Li Y. Temporal and spatial regulation of gene expression mediated by the promoter for the human tissue inhibitor of metalloproteinases-3 (TIMP-3)-encoding gene[J].{H}Development Dynamics,1998,(3):228-237.
  • 10Zreiqat H,Belluoccio D,Smith MM. S100A8 and S100A9 in experimental osteoarthritis[J].{H}Arthritis Research &#x0026; Therapy,2010,(1):R16.

同被引文献52

  • 1郭莹,赵颖海.肿瘤中Fas基因的研究进展[J].广东医学院学报,2014,32(1):91-93. 被引量:5
  • 2Butler RJ, Marchsi S, Royer T, et al. The effect of a subjectspecific amount of lateral wedge on knee osteoarthritis [J]. J orthop Res,2007,25(9) : 1121-1127.
  • 3Thorstensson CA, Henriksson M, yon Porat A, et al. The sffect of eight weeks of exercise on knee adduction moment in early knee osteoarthrlsis-a pilot study [J]. Osteoarthrisis Cartilage,2007, 15 (10) : 1163-1170.
  • 4Spector TD, MacGregor AJ. Risk factors for osteoarthritis: genetics [ J ]. Osteoarthritis Cartilage, 2004,12 Suppl A : S39-S44.
  • 5Ehrlich M, Wang RY. 5-Methylcytosine in eukaryotic DNA[J]. Science, 1981,212(4501 ) : 1350-1357.
  • 6Matlock AJ, Madison D, Lyle WB, et al. Genome-wide DNA methylation study Identifies significant epigenomic changes in osteoarthritic cartilage[J]. Arthritis Rheumatol,2014,66(10) : 2804-2815.
  • 7Brandt KD, Dieppe P, Radin E, et al. Etiopathogenesis of osteoarthritis [J ]. Med Clin North Am, 2009,93 ( 1 ) : 1-24.
  • 8Roach HI, Yamada N, Cheung KS, et al. Association between the abnormal expression of matrix-degrading enzymes by human osteoarthritic chondrocytes and sites in the promoter regions [J] 3110-3124. demethylation of speeifi c CpG Arthritis Rheum, 2005,25 (10) :.
  • 9Ishii HH, Gobe GC ,Yoneyam aJ, et al. Role of p53 ,apoptosis, and cell proliferation in early stage Epstein-Barr virus positive and Negative gastrie carcinomas [J l, J Clin Pathol, 2004,57 (12): 1306-1311.
  • 10Erlaeher L, Maier R, Ullrich R, et al. Differential expression of the protooncogene bel-2 in normal and osteoarthritic human articular cartilage[J]. J Rheumatol, 1995,22(5) :926-931.

引证文献3

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部