Longterm culture of telomerase-transduced rheumatoid arthritis, fibroblast-like synoviocytes display a distinct gene expression pattern

被引:0
作者
Sun, Yubo
Firestein, Gary
Boyle, David
Gruber, Helen
Cheung, Herman
机构
[1] Carolinas Med Ctr, Div Biol, Dept Orthopaed Surg, Charlotte, NC 28232 USA
[2] Univ Calif San Diego, Sch Med, Div Rheumatol Allergy & Immunol, La Jolla, CA 92093 USA
[3] Univ Miami, Dept Biomed Engn, Coral Gables, FL 33124 USA
[4] Vet Affairs Med Ctr, Res Serv, Miami, FL 33125 USA
[5] Vet Affairs Med Ctr, Ctr Geriatr Res Educ & Clin, Miami, FL 33125 USA
关键词
synoviocytes; rheumatoid arthritis; autoantigen; CCL2; CHI3L1; HAPLN1; AGC1; PRG4; telomerase;
D O I
暂无
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objective. To extend the lifespan of rheumatoid arthritis fibroblast-like synoviocytes (RA FLS) using human telomerase catalytic subunit (hTERT) and to test the hypothesis that longterm culture of hTERTRA FLS may display a disease-specific gene expression pattern. Methods. RA 516 FLS were transduced by hTERT and the replicative properties of hTERT-RA 516 FLS were evaluated by repeated expansion. Gene expressions in hTERT-RA 516 FLS (passage 8) were compared with the gene expressions in hTERT-osteoarthritis (OA) 13A FLS (passage 8) by microarrays and RT-PCR. After continuous expansion in culture for an additional 4 months, gene expression was examined again using real-time RT-PCR and microarray. Results. While primary RA 516 FLS stopped dividing after repeated culture for about 120 days, hTERTRA 516 FLS continued to grow at a steady rate. The hTERT-RA 156 FLS displayed a distinct gene expression pattern. different from hTERT-OA 13A FLS. Several putative. autoantigens and cytokine A2/monocyte chemoattractant protein-1 were expressed at significantly higher levels in longterm culture of hTERT-RA 516 FLS. Conclusion. Telomerase-transduced RA FLS offer an alternative cell model for the study of RA and for examination of cellular/genetic alterations in RA FLS. Our findings provide further support for the notion that RA FLS are altered cells.
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页码:1959 / 1970
页数:12
相关论文
共 48 条
  • [31] THE MITOGENIC RESPONSE TO STIMULATION WITH BASIC CALCIUM-PHOSPHATE CRYSTALS IS ACCOMPANIED BY INDUCTION AND SECRETION OF COLLAGENASE IN HUMAN FIBROBLASTS[J]. MCCARTHY, GM;MITCHELL, PG;CHEUNG, HS. ARTHRITIS AND RHEUMATISM, 1991(08)
  • [32] hEST2, the putative human telomerase catalytic subunit gene, is up-regulated in tumor cells and during immortalization[J]. Meyerson, M;Counter, CM;Eaton, EN;Ellisen, LW;Steiner, P;Caddle, SD;Ziaugra, L;Beijersbergen, RL;Davidoff, MJ;Liu, QY;Bacchetti, S;Haber, DA;Weinberg, RA. CELL, 1997(04)
  • [33] Muller-Ladner Ulf, 1995, Current Opinion in Rheumatology, V7, P222, DOI 10.1097/00002281-199505000-00011
  • [34] MullerLadner U, 1996, AM J PATHOL, V149, P1607
  • [35] Regeneration of defects in articular cartilage in rat knee joints by CCN2 (connective tissue growth factor)[J]. Nishida, T;Kubota, S;Kojima, S;Kuboki, T;Nakao, K;Kushibiki, T;Tabata, Y;Takigawa, M. JOURNAL OF BONE AND MINERAL RESEARCH, 2004(08)
  • [36] A new mathematical model for relative quantification in real-time RT-PCR[J]. Pfaffl, MW. NUCLEIC ACIDS RESEARCH, 2001(09)
  • [37] Lymphoid chemokine B cell-attracting chemokine-1 (CXCL13) is expressed in germinal center of ectopic lymphoid follicles within the synovium of chronic arthritis patients[J]. Shi, KR;Hayashida, K;Kaneko, M;Hashimoto, J;Tomita, T;Lipsky, PE;Yoshikawa, H;Ochi, T. JOURNAL OF IMMUNOLOGY, 2001(01)
  • [38] Localization of MHC class II/human cartilage glycoprotein-39 complexes in synovia of rheumatoid arthritis patients using complex-specific monoclonal antibodies[J]. Steenbakkers, PGA;Baeten, D;Rovers, E;Veys, EM;Rijnders, AWM;Meijerink, J;De Keyser, F;Boots, AMH. JOURNAL OF IMMUNOLOGY, 2003(11)
  • [39] Telomerase-transduced osteoarthritic fibroblast-like synoviocyte cell line[J]. Sun, YB;Firestein, GS;Wenger, L;Huang, CYC;Cheung, HS. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2004(04)
  • [40] Lymphoid neogenesis in rheumatoid synovitis[J]. Takemura, S;Braun, A;Crowson, C;Kurtin, PJ;Cofield, RH;O'Fallon, WM;Goronzy, JJ;Weyand, CM. JOURNAL OF IMMUNOLOGY, 2001(02)