Skip to main content


Log in

Comparison of the expression profile of apoptosis-associated genes in rheumatoid arthritis and osteoarthritis

  • Original Article
  • Published:
Rheumatology International Aims and scope Submit manuscript


The purpose of this study was to employ microarray analysis to evaluate differential gene expression in synovial tissue samples obtained from patients with rheumatoid arthritis (RA) or osteoarthritis (OA) to study the expression profile of apoptosis-associated genes in these tissues. Four samples were obtained from RA-affected patients and three from osteoarthritis patients. After total RNA was extracted from synovial tissue, the RNA was processed using two-cycle target labeling, followed by hybridization and scanning procedure. The GeneChip Human Genome U133 Plus 2.0 containing 900471 gene loci was used and eight genes associated with apoptosis were identified with a selected p value <0.05 and a twofold change in expression in rheumatoid samples compared to osteoarthritis tissues. Anti-apoptotic genes were generally upregulated whereas apoptotic genes were downregulated suggesting that these genes may play a role in the pathogenesis of RA. Furthermore, these genes may serve as novel therapeutic targets for the treatment of RA.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others


  1. Gay S, Gay RE, Koopman WJ (1993) Molecular and cellular mechanism of joint destruction in rheumatoid arthritis: two cellar mechanisms explain joint destruction. Ann Rheum Dis 52:39–47

    Article  Google Scholar 

  2. MacKenzie NM (2006) New therapeutics that treat rheumatoid arthritis by blocking T-cell activation. Drug Discov Today 11:952–956

    Article  PubMed  CAS  Google Scholar 

  3. Hui A, Kulkarni GV, Hunter WL, McCulloch CA, Cruz TF (1997) Paclitaxel selectively induces mitotic arrest and apoptosis in proliferating bovine synoviocytes. Arthritis Rheum 40:1073–1084

    Article  PubMed  CAS  Google Scholar 

  4. Nakajima T, Aono H, Hasunuma T, Yamamoto K, Shirai T, Hirohata K, Nishioka K (1995) Apoptosis and functional Fas antigen in rheumatoid arthritis synoviocytes. Arthritis Rheum 38:485–491

    Article  PubMed  CAS  Google Scholar 

  5. Ceponis A, Hietanen J, Tamulaitiene M, Partsch G, Pätiälä H, Konttinen YT (1999) A comparative quantitative morphometric study of cell apoptosis in synovial membranes in psoriatic, reactive and rheumatoid arthritis. Rheumatology (Oxford) 38:431–440

    Article  CAS  Google Scholar 

  6. Kobayashi T, Okamoto K, Kobata T, Hasumuna T, Nishioka K (1999) Apomodulation as a novel therapeutic concept for the regulation of apoptosis in rheumatoid synoviocytes. Curr Opin Rheumatol 11:188–193

    Article  PubMed  CAS  Google Scholar 

  7. Wolfe F, Michaud K (2007) Resistance of rheumatoid arthritis patients to changing therapy: discordance between disease activity and patients’ treatment choices. Arthritis Rheum 56:2135–2142 [Epub ahead of print]

    Article  PubMed  CAS  Google Scholar 

  8. Bernatsky S, Hudson M, Suissa S (2007) Anti-rheumatic drug use and risk of serious infections in rheumatoid arthritis. Rheumatology (Oxford) 46:1157–1160

    Article  CAS  Google Scholar 

  9. Buch MH, Bingham SJ, Bryer D, Emery P (2007) Long-term infliximab treatment in rheumatoid arthritis: subsequent outcome of initial responders. Rheumatology (Oxford) 46:1153–1156

    Article  CAS  Google Scholar 

  10. Mountz JD, Wu J, Cheng H, Zhou T (1994) Autoimmune disease: a problem of defective apoptosis. Science 37:1415–1420

    CAS  Google Scholar 

  11. Ogawa N, Dang H, Hald N (1995) Apoptosis and autoimmunity. J Antoimmun 8:1–19

    Article  CAS  Google Scholar 

  12. Firestein GS, Nguyen K, Aupperle KR, Yeo M, Boyle DL, Zvaifler NJ (1996) Apoptosis in rheumatoid arthritis: p53 overexpression in rheumatoid arthritis synovium. Am J Pathol 149:2143–2151

    PubMed  CAS  Google Scholar 

  13. Triplett JW, Pavalko FM (2006) Disruption of alpha-actinin–integrin interactions at focal adhesions renders osteoblasts susceptible to apoptosis. Am J Physiol Cell Physiol 291:C909–C921

    Article  PubMed  CAS  Google Scholar 

  14. Sasaki S, Nakamura T, Arakawa H, Mori M, Watanabe T, Nagawa H, Croce CM (2002) Isolation and characterization of a novel gene, hRFI, preferentially expressed in esophageal cancer. Oncogene 21:5024–5030

    Article  PubMed  CAS  Google Scholar 

  15. Sasaki S, Watanabe T, Konishi T, Kitayama J, Nagawa H (2004) Effects of expression of hRFI on adenoma formation and tumor progression in colorectal adenoma––carcinoma sequence. J Exp Clin Cancer Res 23:507–512

    PubMed  CAS  Google Scholar 

  16. Galvan V, Logvinova A, Sperandio S, Ichijo H, Bredesen DE (2003) Type 1 insulin-like growth factor receptor (IGF-IR) signaling inhibits apoptosis signal-regulating kinase 1 (ASK1). J Biol Chem 278:13325–13332

    Article  PubMed  CAS  Google Scholar 

  17. Zwerina J, Hayer S, Redlich K, Bobacz K, Kollias G, Smolen JS, Schett G (2006) Activation of p38 MAPK is a key step in tumor necrosis factor-mediated inflammatory bone destruction. Arthritis Rheum 54:463–472

    Article  PubMed  CAS  Google Scholar 

  18. Nakajima K, Hirose H, Taniguchi M, Kurashina H, Arasaki K, Nagahama M, Tani K, Yamamoto A, Tagaya M (2004) Involvement of BNIP1 in apoptosis and endoplasmic reticulum membrane fusion. EMBO J 23:3216–3226

    Article  PubMed  CAS  Google Scholar 

  19. Mishra S, Murphy LJ (2006) The p53 oncoprotein is a substrate for tissue transglutaminase kinase activity. Biochem Biophys Res Commun 339:726–730

    Article  PubMed  CAS  Google Scholar 

  20. Davila E, Kang YM, Park YW, Sawai H, He X, Pryshchep S, Goronzy JJ, Weyand CM (2005) Cell-based immunotherapy with suppressor CD8 + T cells in rheumatoid arthritis. J Immunol 174:7292–7301

    PubMed  CAS  Google Scholar 

  21. Ehinger M, Vestberg M, Johansson AC, Johannesson M, Svensson A, Holmdahl R (2001) Influence of CD4 or CD8 deficiency on collagen-induced arthritis. J Immunol 103:291–300

    Article  CAS  Google Scholar 

  22. Taneja V, Taneja N, Paisansinsup T, Behrens M, Griffiths M, Luthra H, David CS (2002) CD4 and CD8 T cells in susceptibility/protection to collagen-induced arthritis in HLA-DQ8-transgenic mice: implications for rheumatoid arthritis. J Immunol 168:5867–5875

    PubMed  CAS  Google Scholar 

  23. Mohan K, Pinto D, Issekutz TB (2003) Identification of tissue transglutaminase as a novel molecule involved in human CD8+ T cell transendothelial migration. J Immunol 171:3179–3186

    PubMed  CAS  Google Scholar 

  24. Fan Z, Beresford PJ, Zhang D, Xu Z, Novina CD, Yoshida A, Pommier Y, Lieberman J (2003) Cleaving the oxidative repair protein Ape1 enhances cell death mediated by granzyme A. Nat Immunol 4:106–108

    Article  Google Scholar 

  25. Su HP, Nakada-Tsukui K, Tosello-Trampont AC, Li Y, Bu G, Henson PM, Ravichandran KS (2002) Interaction of CED-6/GULP, an adapter protein involved in engulfment of apoptotic cells with CED-1 and CD91/low density lipoprotein receptor-related protein (LRP). J Biol Chem 277:11772–11779

    Article  PubMed  CAS  Google Scholar 

  26. Sharfe N, Dadi HK, Shahar M, Roifman CM (1997) Human immune disorder arising from mutation of the alpha chain of the interleukin-2 receptor. Proc Natl Acad Sci USA 4:3168–3171

    Article  Google Scholar 

Download references


This work was supported by the Department of Medical Research of Guangzhou LiuHuaQiao Hospital, GeneTech Biotechnology Limited Company and a fund from Guangdong Province key technology research projects (No. 200434001010).

Author information

Authors and Affiliations


Corresponding author

Correspondence to Huang Qingchun.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Qingchun, H., Runyue, H., LiGang, J. et al. Comparison of the expression profile of apoptosis-associated genes in rheumatoid arthritis and osteoarthritis. Rheumatol Int 28, 697–701 (2008).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: