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Inflammatory synovial fluid microenvironment drives primary human chondrocytes to actively take part in inflammatory joint diseases

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Abstract

The role of human chondrocytes in the pathogenesis of cartilage degradation in rheumatic joint diseases has presently gained increasing interest. An active chondrocyte participation in local inflammation may play a role in the initiation and progression of inflammatory joint diseases and in a disruption of cartilage repair mechanisms resulting in cartilage degradation. In the present study, we hypothesized that inflammatory synovial fluid triggers human chondrocytes to actively take part in inflammatory processes in rheumatic joint diseases. Primary human chondrocytes were incubated in synovial fluids gained from patients with rheumatoid arthritis, psoriasis arthritis and reactive arthritis. The detection of vital cell numbers was determined by using Casy Cell Counter System. Apoptosis was measured by Annexin-V and 7AAD staining. Cytokine and chemokine secretion was determined by a multiplex suspension array. Detection of vital cells showed a highly significant decrease in chondrocyte numbers. Flow cytometry demonstrated a significant increase in apoptotic chondrocytes after the incubation. An active secretion of cytokines such as MCP-1 and MIF by chondrocytes was observed. The inflammatory synovial fluid microenvironment mediates apoptosis and cell death of chondrocytes. Moreover, in terms of cytokine secretion, it also induces an active participation of chondrocytes in ongoing inflammation.

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References

  1. Kim HA, Song YW. Apoptotic chondrocyte death in rheumatoid arthritis. Arthritis Rheum. 1999;42:1528–37.

    Article  PubMed  CAS  Google Scholar 

  2. Matsumoto S, Muller-Ladner U, Gay RE, Nishioka K, Gay S. Ultrastructural demonstration of apoptosis, Fas and Bcl-2 expression of rheumatoid synovial fibroblasts. J Rheumatol. 1996;23:1345–52.

    PubMed  CAS  Google Scholar 

  3. Koch AE. Chemokines and their receptors in rheumatoid arthritis: future targets? Arthritis Rheum. 2005;52:710–21.

    Article  PubMed  Google Scholar 

  4. Szekanecz Z, Kim J, Koch AE. Chemokines and chemokine receptors in rheumatoid arthritis. Semin Immunol. 2003;15:15–21.

    Article  PubMed  CAS  Google Scholar 

  5. Szekanecz Z, Szucs G, Szanto S, Koch AE. Chemokines in rheumatic diseases. Curr Drug Targets. 2006;7:91–102.

    Article  PubMed  CAS  Google Scholar 

  6. Vergunst CE, Tak PP. Chemokines: their role in rheumatoid arthritis. Curr Rheumatol Rep. 2005;7:382–8.

    Article  PubMed  CAS  Google Scholar 

  7. Braun J, Brandt J, Listing J, Zink A, Alten R, Burmester G, Golder W, Gromnica-Ihle E, Kellner H, Schneider M, Sorensen H, Zeidler H, Reddig J, Sieper J. Long-term efficacy and safety of infliximab in the treatment of ankylosing spondylitis: an open, observational, extension study of a three-month, randomized, placebo-controlled trial. Arthritis Rheum. 2003;48:2224–33.

    Article  PubMed  CAS  Google Scholar 

  8. Braun J, Brandt J, Listing J, Zink A, Alten R, Golder W, Gromnica-Ihle E, Kellner H, Krause A, Schneider M, Sorensen H, Zeidler H, Thriene W, Sieper J. Treatment of active ankylosing spondylitis with infliximab: a randomised controlled multicentre trial. Lancet. 2002;359:1187–93.

    Article  PubMed  CAS  Google Scholar 

  9. Confavreux CB, Chapurlat RD. Systemic bone effects of biologic therapies in rheumatoid arthritis and ankylosing spondylitis. Osteoporos Int 2010.

  10. Rau R. Efficacy of methotrexate in comparison to biologics in rheumatoid arthritis. Clin Exp Rheumatol. 2010;28:S58–64.

    PubMed  CAS  Google Scholar 

  11. Singh JA, Christensen R, Wells GA, Suarez-Almazor ME, Buchbinder R, Lopez-Olivo MA, Ghogomu ET, Tugwell P. A network meta-analysis of randomized controlled trials of biologics for rheumatoid arthritis: a Cochrane overview. CMAJ. 2009;181:787–96.

    Article  PubMed  Google Scholar 

  12. Virkki LM, Sumathikutty BC, Aarnio M, Valleala H, Heikkila R, Kauppi M, Karstila K, Pirila L, Ekman P, Salomaa S, Romu M, Seppala J, Niinisalo H, Konttinen YT, Nordstrom DC. Biological therapy for psoriatic arthritis in clinical practice: outcomes up to 2 years. J Rheumatol. 2010;37:2362–8.

    Article  PubMed  Google Scholar 

  13. Yokota S, Kishimoto T. Tocilizumab: molecular intervention therapy in children with systemic juvenile idiopathic arthritis. Expert Rev Clin Immunol. 2010;6:735–43.

    Article  PubMed  CAS  Google Scholar 

  14. Deffaud J, Kirchmeyer M, Domagala F, Ficheux H, Netter P, Bianchi A, Jouzeau JY. Modulatory effect of rhein on IL-1alpha-induced responses in human chondrocytes: a comparative study between antibody microarrays and specific ELISAs. Biorheology. 2008;45:439–55.

    PubMed  CAS  Google Scholar 

  15. David F, Farley J, Huang H, Lavoie JP, Laverty S. Cytokine and chemokine gene expression of IL-1beta stimulated equine articular chondrocytes. Vet Surg. 2007;36:221–7.

    Article  PubMed  Google Scholar 

  16. Sandell LJ, Xing X, Franz C, Davies S, Chang LW, Patra D. Exuberant expression of chemokine genes by adult human articular chondrocytes in response to IL-1beta. Osteoarthritis Cartilage. 2008;16:1560–71.

    Article  PubMed  CAS  Google Scholar 

  17. Röhner E, Detert J, Kolar P, Hocke A, N’Guessan P, Matziolis G, Kanitz V, Bernimoulin JP, Kielbassa A, Burmester GR, Buttgereit F, Pischon N. Induced apoptosis of chondrocytes by Porphyromonas gingivalis as a possible pathway for cartilage loss in rheumatoid arthritis. Calcif Tissue Int. 2010;87:333–40.

    Article  PubMed  Google Scholar 

  18. Butrimiene I, Jarmalaite S, Ranceva J, Venalis A, Jasiuleviciute L, Zvirbliene A. Different cytokine profiles in patients with chronic and acute reactive arthritis. Rheumatology (Oxford). 2004;43:1300–4.

    Article  CAS  Google Scholar 

  19. Feldmann M, Maini SR. Role of cytokines in rheumatoid arthritis: an education in pathophysiology and therapeutics. Immunol Rev. 2008;223:7–19.

    Article  PubMed  CAS  Google Scholar 

  20. Fernandes JC, Martel-Pelletier J, Pelletier JP. The role of cytokines in osteoarthritis pathophysiology. Biorheology. 2002;39:237–46.

    PubMed  CAS  Google Scholar 

  21. Uppal SS, Raghupathy R, Hayat SJ, Longenecker JC, Abraham M, Rawoot P. Disease activity and cytokine production in mitogen-stimulated peripheral blood mononuclear cells from patients with rheumatoid arthritis. Med Princ Pract. 2010;19:33–9.

    Article  PubMed  Google Scholar 

  22. Hengartner MO. The biochemistry of apoptosis. Nature. 2000;407:770–6.

    Article  PubMed  CAS  Google Scholar 

  23. Szekanecz Z, Koch AE. Mechanisms of disease: angiogenesis in inflammatory diseases. Nat Clin Pract Rheumatol. 2007;3:635–43.

    Article  PubMed  CAS  Google Scholar 

  24. Folkman J, Klagsbrun M. Angiogenic factors. Science. 1987;235:442–7.

    Article  PubMed  CAS  Google Scholar 

  25. Boehm T, Folkman J, Browder T, O’Reilly MS. Antiangiogenic therapy of experimental cancer does not induce acquired drug resistance. Nature. 1997;390:404–7.

    Article  PubMed  CAS  Google Scholar 

  26. Fearon U, Veale DJ. Angiogenesis in arthritis: methodological and analytical details. Methods Mol Med. 2007;135:343–57.

    Article  PubMed  Google Scholar 

  27. Koch AE. Review: angiogenesis: implications for rheumatoid arthritis. Arthritis Rheum. 1998;41:951–62.

    Article  PubMed  CAS  Google Scholar 

  28. Lainer-Carr D, Brahn E. Angiogenesis inhibition as a therapeutic approach for inflammatory synovitis. Nat Clin Pract Rheumatol. 2007;3:434–42.

    Article  PubMed  CAS  Google Scholar 

  29. Veale DJ, Fearon U. Inhibition of angiogenic pathways in rheumatoid arthritis: potential for therapeutic targeting. Best Pract Res Clin Rheumatol. 2006;20:941–7.

    Article  PubMed  CAS  Google Scholar 

  30. Tanabe M, Ochi T, Tomita T, Suzuki R, Sakata T, Shimaoka Y, Nakagawa S, Ono K. Remarkable elevation of interleukin 6 and interleukin 8 levels in the bone marrow serum of patients with rheumatoid arthritis. J Rheumatol. 1994;21:830–5.

    PubMed  CAS  Google Scholar 

  31. Ellingsen T, Buus A, Stengaard-Pedersen K. Plasma monocyte chemoattractant protein 1 is a marker for joint inflammation in rheumatoid arthritis. J Rheumatol. 2001;28:41–6.

    PubMed  CAS  Google Scholar 

  32. Weber C, Belge KU, von Hundelshausen P, Draude G, Steppich B, Mack M, Frankenberger M, Weber KS, Ziegler-Heitbrock HW. Differential chemokine receptor expression and function in human monocyte subpopulations. J Leukoc Biol. 2000;67:699–704.

    PubMed  CAS  Google Scholar 

  33. Valente AJ, Graves DT, Vialle-Valentin CE, Delgado R, Schwartz CJ. Purification of a monocyte chemotactic factor secreted by nonhuman primate vascular cells in culture. Biochemistry. 1988;27:4162–8.

    Article  PubMed  CAS  Google Scholar 

  34. Hayashida K, Nanki T, Girschick H, Yavuz S, Ochi T, Lipsky PE. Synovial stromal cells from rheumatoid arthritis patients attract monocytes by producing MCP-1 and IL-8. Arthritis Res. 2001;3:118–26.

    Article  PubMed  CAS  Google Scholar 

  35. Kageyama Y, Kobayashi H, Kato N, Shimazu M. Etanercept reduces the serum levels of macrophage chemotactic protein-1 in patients with rheumatoid arthritis. Mod Rheumatol. 2009;19:372–8.

    Article  PubMed  CAS  Google Scholar 

  36. Bacher M, Metz CN, Calandra T, Mayer K, Chesney J, Lohoff M, Gemsa D, Donnelly T, Bucala R. An essential regulatory role for macrophage migration inhibitory factor in T-cell activation. Proc Natl Acad Sci USA. 1996;93:7849–54.

    Article  PubMed  CAS  Google Scholar 

  37. Calandra T, Bernhagen J, Mitchell RA, Bucala R. The macrophage is an important and previously unrecognized source of macrophage migration inhibitory factor. J Exp Med. 1994;179:1895–902.

    Article  PubMed  CAS  Google Scholar 

  38. Rossi AG, Haslett C, Hirani N, Greening AP, Rahman I, Metz CN, Bucala R, Donnelly SC. Human circulating eosinophils secrete macrophage migration inhibitory factor (MIF). Potential role in asthma. J Clin Invest. 1998;101:2869–74.

    Article  PubMed  CAS  Google Scholar 

  39. Ayoub S, Hickey MJ, Morand EF. Mechanisms of disease: macrophage migration inhibitory factor in SLE, RA and atherosclerosis. Nat Clin Pract Rheumatol. 2008;4:98–105.

    Article  PubMed  CAS  Google Scholar 

  40. Santos LL, Morand EF. Macrophage migration inhibitory factor: a key cytokine in RA, SLE and atherosclerosis. Clin Chim Acta. 2009;399:1–7.

    Article  PubMed  CAS  Google Scholar 

  41. Kim HR, Park MK, Cho ML, Yoon CH, Lee SH, Park SH, Leng L, Bucala R, Kang I, Choe J, Kim HY. Macrophage migration inhibitory factor upregulates angiogenic factors and correlates with clinical measures in rheumatoid arthritis. J Rheumatol. 2007;34:927–36.

    PubMed  CAS  Google Scholar 

  42. Morand EF, Leech M, Weedon H, Metz C, Bucala R, Smith MD. Macrophage migration inhibitory factor in rheumatoid arthritis: clinical correlations. Rheumatology (Oxford). 2002;41:558–62.

    Article  CAS  Google Scholar 

  43. Onodera S, Nishihira J, Yamazaki M, Ishibashi T, Minami A. Increased expression of macrophage migration inhibitory factor during fracture healing in rats. Histochem Cell Biol. 2004;121:209–17.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

We would like to thank Manuela Jakstadt for brilliant technical assistance.

Conflict of interest

The authors have no proprietary, financial, professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the results and views presented in this article.

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Authors and Affiliations

  1. Department of Traumatology and Orthopedics, Charité University Hospital, Berlin, Germany

    Eric Röhner, Georg Matziolis, Carsten Perka & Bernd Füchtmeier

  2. Department of Rheumatology and Clinical Immunology, Charité University Hospital, Charitéplatz 1, 10117, Berlin, Germany

    Timo Gaber, Gerd-Rüdiger Burmester, Frank Buttgereit & Paula Hoff

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  1. Eric Röhner
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  2. Georg Matziolis
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  3. Carsten Perka
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Correspondence to Paula Hoff.

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Röhner, E., Matziolis, G., Perka, C. et al. Inflammatory synovial fluid microenvironment drives primary human chondrocytes to actively take part in inflammatory joint diseases. Immunol Res 52, 169–175 (2012). https://doi.org/10.1007/s12026-011-8247-5

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  • DOI: https://doi.org/10.1007/s12026-011-8247-5

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