Skip to main content

Advertisement

SpringerLink
Log in

Local cell proliferation in rheumatoid synovial tissue: analysis by cyclin expression

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

Abstract

The immunohistochemical staining of cyclins was done to evaluate the proliferating cells in synovial tissue of rheumatoid arthritis (RA). Synovial specimens obtained from 18 patients with RA, 12 with osteoarthritis (OA), and 8 with traumatic arthritis (TA) were used for immunostaining of cyclins A and B1 and proliferating cell nuclear antigen (PCNA). The positive cells in lining layer (synoviocytes) and sublining layer (lymphoid and nonlymphoid cells) were counted. Moreover, the relationship between the frequency of their positive cells and clinical data of RA patients was analyzed statistically. In general, cyclin-A-, cyclin-B1-, and PCNA-positive cells in RA were more frequently observed as compared with those in OA and TA. Significant differences were found between RA and OA or TA in cyclin-A-, cyclin-B1-, and PCNA-positive sublining lymphoid cells, between RA and OA or TA in cyclin-B1- and PCNA-positive sublining nonlymphoid cells, and between RA and OA in cyclin-B1-positive synoviocytes. The ratio of cyclin-A- or cyclin-B1-positive cells per PCNA-positive cells was significantly higher in sublining lymphoid cells in RA than TA and in sublining lymphoid and nonlymphoid cells of RA than OA or TA. Moreover, a better relationship was observed between the frequency of cyclin-A-positive synoviocytes and age and between cyclin-A-positive sublining nonlymphoid cells and duration of the disease in RA patients. Our data demonstrated clearly that synoviocytes, as well as sublining lymphoid and nonlymphoid cells, could divide in situ, and more frequent cell division and a higher ratio of cyclin-A- or cyclin-B1-positive/PCNA-positive sublining cells could occur in RA than OA and TA.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Newman AP (1993) Synovectomy. In: Kelly WN, Harris ED, Ruddy S, Sledge CB (eds) Textbook of rheumatology, 4th edn. Saunders, Philadelphia, pp 649–670

    Google Scholar 

  2. Gardner EL (1992) Rheumatoid arthritis: pathogenesis, experimental studies and complications. In: Arnold E (ed) Pathological basis of the connective tissue diseases, 1st edn. London, pp 527–567

  3. Handa K, Yamakawa M, Takeda H, Kimura S, Takahashi T (1999) Expression of cell cycle markers in colorectal carcinoma: superiority of cyclin A as an indicator of poor diagnosis. Int J Cancer 84:225–233

    Article  PubMed  CAS  Google Scholar 

  4. Nonomura Y, Kohsaka H, Nagasaka K, Miyasaka N (2003) Gene transfer of a cell cycle modulator exerts anti-inflammatory effects in the treatment of arthritis. J Immunol 171:4913–4919

    PubMed  CAS  Google Scholar 

  5. Ohrui H, Yamakawa M, Imai Y (1997) Proliferation and apoptosis of follicular lymphocytes: relationship to follicular dendritic cell-associated clusters. Immunology 90:489–495

    Article  PubMed  Google Scholar 

  6. Bukholm IR, Bukholm G, Holm R, Nesland JM (2003) Association between histology grade, expression of HsMCM2, and cyclin A in human invasive breast carcinomas. J Clin Pathol 56:368–373

    Article  PubMed  CAS  Google Scholar 

  7. Qu Z, Garcia CH, O’Rourke LM, Planck SR, Kohli M, Rosenbaum JT (1994) Local proliferation of fibroblast-like synoviocytes contributes to synovial hyperplasia: results of proliferating cell nuclear antigen/cyclin, c-myc, and nucleolar organizer region staining. Arthritis Rheum 37:212–220

    PubMed  CAS  Google Scholar 

  8. Migita K, Tanaka F, Yamasaki S, Shibatomi K, Ida H, Kawakami A, Aoyagi T, Kawabe Y, Eguchi K (2001) Regulation of rheumatoid synoviocyte proliferation by endogenous p53 induction. Clin Exp Immunol 126:334–338

    Article  PubMed  CAS  Google Scholar 

  9. Kirkham B, Portek I, Lee CS, Stavros B, Lenarczyk A, Lassere M, Edmonds J (1999) Intraarticular variability of synovial membrane histology, immunohistology, and cytokine mRNA expression in patients with rheumatoid arthritis. J Rheumatol 27:777–784

    Google Scholar 

  10. Scott IS, Morris LS, Bird K, Davies RJ, Vowler SL, Rushbrook SM, Marshall AE, Laskey RA, Miller R, Arends MJ, Coleman N (2003) A novel immunohistochemical method to estimate cell-cycle phase distribution in archival tissue: implications for the prediction of outcome in colorectal cancer. J Pathol 201:187–197

    Article  PubMed  Google Scholar 

  11. Michels JJ, Duigou F, Marnay J, Henry-Amar M, Delozier T, Denoux Chasle J (2003) Flow cytometry and quantitative immunohistochemical study of cell cycle regulation proteins in invasive breast carcinoma. Cancer 97:1376–1386

    Article  PubMed  Google Scholar 

  12. Guerrero C, Martin-Encabo S, Ferrnandez-Medarde A, Santos E (2004) C3G-mediated suppression of oncogene-induced focus formation in fibroblasts involves inhibition of ERK activation, cyclin A expression and alteration of anchorage-independent growth. Oncogene 23:4885–4893

    Article  PubMed  CAS  Google Scholar 

  13. Ji P, Agrawal S, Diederichs S, Baumer N, Becker A, Cauvet T, Kowski S, Berger C, Welte K, Berdel WE, Serve H, Muller-Tidow C (2005) Cyclin A1, the alternative A-type cyclin, contribute to G1/S cell cycle progression in somatic cells. Oncogene 14:2739–2744

    Article  CAS  Google Scholar 

  14. Kurose A, Yoshida W, Yoshida M, Sawai T (2001) Effects of paclitaxel on cultured synovial cells from patients with rheumatoid arthritis. Cytometry 44:349–354

    Article  PubMed  CAS  Google Scholar 

  15. Moore JD, Kirk JA, Hunt T (2003) Unmasking the S-phase-promoting potential of cyclin B1. Science 300:987–990

    Article  PubMed  CAS  Google Scholar 

  16. Parker MH, Hussain F, Wickramaratna A, Olsen I (2004) The immunosuppressant and hyperplasia-induced drug cyclosporin A regulates the cell cycle and cyclin B1 gene expression in gingival fibroblasts in vitro. Cell Tissue Res 317:221–225

    PubMed  Google Scholar 

  17. Zeng H, Davis CD (2003) Down-regulation of proliferation cell nuclear antigen gene expression occurs during cell cycle arrest induced by human fecal water in colonic HT-29 cells. J Nutr 133:2682–2687

    PubMed  CAS  Google Scholar 

  18. Yamasaki S, Kawakami A, Nakashima T, Nakamura H, Kamachi H, Honda S, Hirai Y et al (2001) Importance of NF-kappa B in rheumatoid synovial tissues: in situ NF-kappa B expression and in vitro study using cultured synovial cells. Ann Rheum Dis 60:678–684

    Article  PubMed  CAS  Google Scholar 

  19. Uchida T, Nakashima M, Hirota Y, Miyazaki Y, Tsukazaki T, Shindo H (2000) Immunohistochemical localization of protein tyrosine kinase receptor Tie-1 and Tie-2 in synovial tissue of rheumatoid arthritis: correlation with angiogenesis and synovial proliferation. Ann Rheum Dis 59:607–614

    Article  PubMed  CAS  Google Scholar 

  20. Sugiyama M, Tsukazaki T, Yonekura A, Matsuzaki S, Yamashits S, Iwasaki K (1996) Localization of apoptosis and expression of apoptosis related proteins in the synovium of patients with rheumatoid arthritis. Ann Rheum Dis 55:442–449

    Article  PubMed  CAS  Google Scholar 

  21. Tanaka Y, Nomi M, Fujii K, Hubscher S, Maruo A, Matsumoto S, Awazu Y, Saito K, Eto S, Minami Y (2000) Intercellular adhesion molecule 1 underlies the functional heterogeneity of synovial cells in patients with rheumatoid arthritis: involvement of cell cycle machinery. Arthritis Rheum 43:2513–2522

    Article  PubMed  CAS  Google Scholar 

  22. Perlman H, Pagliari LJ, Volin MV (2001) Regulation of apoptosis and cell cycle activity in rheumatoid arthritis. Curr Mol Med 1:597–608

    Article  PubMed  CAS  Google Scholar 

  23. Bai M, Papoudou-Bai A, Kitsoulos P, Horianopoulos N, Kamina S, Agnantis NJ, Kanavaros P (2005) Cell cycle and apoptosis deregulation in classical Hodgkin lymphomas. In Vivo 18:439–453

    Google Scholar 

  24. Harding H, Giles N, Burgess A, Hancock JF, Gabrielli BG (2003) Mechanism of mitosis-specific activation of MEK1. J Cell Biochem 278:16747–16754

    CAS  Google Scholar 

  25. Vairapandi M (2004) Characterization of DNA demethylation in normal and cancerous cell lines and the regulatory role of cell cycle proteins in human DNA demethylase activity. J Cell Biochem 91:572–583

    Article  PubMed  CAS  Google Scholar 

  26. Jürchott K, Bergmann S, Stein U, Walther W, Janz M, Mann I, Piaggio G, Fietze E, Dietel M, Royer HD (2003) YB-1 as a cell cycle-regulated transcription factor facilitation cyclin A and cyclin B1 gene expression. J Cell Biochem 278:27988–27996

    Google Scholar 

  27. Golias CH (2004) Charalabopoulos A, Charalabopoulos K. Cell proliferation and cell cycle control: a mini review. Int J Clin Pract 58:1134–1141

    Article  PubMed  CAS  Google Scholar 

  28. Helmchen B, Weckauf H, Ehemann V, Wittmann I, Meyer-Scholten C, Berger I (2005) Expression pattern of cell cycle-related gene products in synovial stroma and synovial lining in active and quiescent stages of rheumatoid arthritis. Histol Histopathol 20:365–372

    PubMed  CAS  Google Scholar 

  29. Harrison ML, Kim CA, Silverberg M, Pagrt SA (2005) Does age bias the aggressive treatment of elderly patients with rheumatoid arthritis? J Rheumatol 32:1243–1248

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Orthopedic Surgery, Rheumatic Center, Niigata Prefectural Senami Hospital, 2-4-15, Senami-Onsen, Murakami, 958-8555, Niigata, Japan

    Chikako Takahashi Tohyama, Akira Murasawa, Kiyoshi Nakazono & Hajime Ishikawa

  2. Department of Pathology, Yamagata University School of Medicine, 2-2-2, Iida-Nishi, Yamagata, 990-9585, Japan

    Mitsunori Yamakawa

Authors
  1. Chikako Takahashi Tohyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mitsunori Yamakawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Akira Murasawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kiyoshi Nakazono
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hajime Ishikawa
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Chikako Takahashi Tohyama.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Takahashi Tohyama, C., Yamakawa, M., Murasawa, A. et al. Local cell proliferation in rheumatoid synovial tissue: analysis by cyclin expression. Clin Rheumatol 25, 801–806 (2006). https://doi.org/10.1007/s10067-005-0189-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10067-005-0189-7

Keywords

Search

Navigation