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Persisting High Levels of Synovial Fluid Markers after Cartilage Repair

A Pilot Study

  • Original Article
  • Published:
Clinical Orthopaedics and Related Research

Abstract

Local attempts to repair a cartilage lesion could cause increased levels of anabolic and catabolic factors in the synovial fluid. After repair with regenerated cartilage, the homeostasis of the cartilage ideally would return to normal. In this pilot study, we first hypothesized levels of synovial fluid markers would be higher in patients with cartilage lesions than in patients with no cartilage lesions, and then we hypothesized the levels of synovial fluid markers would decrease after cartilage repair. We collected synovial fluid samples from 10 patients before autologous chondrocyte transplantation of the knee. One year later, a second set of samples was collected and arthroscopic evaluation of the repair site was performed. Fifteen patients undergoing knee arthroscopy for various symptoms but with no apparent cartilage lesions served as control subjects. We measured synovial fluid matrix metalloproteinase-3 (MMP-3) and insulinlike growth factor-I (IGF-I) concentrations with specific activity and enzyme-linked immunosorbent assays, respectively. The levels of MMP-3 and IGF-I were higher in patients having cartilage lesions than in control subjects with no cartilage lesions. One year after cartilage repair, the lesions were filled with repair tissue, but the levels of MMP-3 and IGF-I remained elevated, indicating either graft remodeling or early degeneration.

Level of Evidence: Level III, prognostic study. See the Guidelines for Authors for a complete description of levels of evidence.

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References

  1. Åroen A, Loken S, Heir S, Alvik E, Ekeland A, Granlund OG, Engebretsen L. Articular cartilage lesions in 993 consecutive knee arthroscopies. Am J Sports Med. 2004;32:211–215.

    Article  PubMed  Google Scholar 

  2. Bobacz K, Maier R, Fialka C, Ekhart H, Woloszczuk W, Geyer G, Erlacher L, Smolen J, Graninger WB. Is pro-matrix metalloproteinase-3 a marker for posttraumatic cartilage degradation? Osteoarthritis Cartilage. 2003;11:665–672.

    Article  PubMed  CAS  Google Scholar 

  3. Brittberg M, Lindahl A, Nilsson A, Ohlsson C, Isaksson O, Peterson L. Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation. N Engl J Med. 1994;331:889–895.

    Article  PubMed  CAS  Google Scholar 

  4. Brittberg M, Nilsson A, Lindahl A, Ohlsson L, Peterson L. Rabbit articular cartilage defects treated with autologous cultured chondrocytes. Clin Orthop Relat Res. 1996;326:270–283.

    Article  PubMed  Google Scholar 

  5. Dahlberg L, Friden T, Roos H, Lark MW, Lohmander LS. A longitudinal study of cartilage matrix metabolism in patients with cruciate ligament rupture: synovial fluid concentrations of aggrecan fragments, stromelysin–1 and tissue inhibitor of metalloproteinase-1. Br J Rheumatol. 1994;33:1107–1111.

    Article  PubMed  CAS  Google Scholar 

  6. Doré S, Pelletier JP, DiBattista JA, Tardif G, Brazeau P, Martel-Pelletier J. Human osteoarthritic chondrocytes possess an increased number of insulin-like growth factor 1 binding sites but are unresponsive to its stimulation: possible role of IGF-1-binding proteins. Arthritis Rheum. 1994;37:253–263.

    Article  PubMed  Google Scholar 

  7. Efron B, Tibshirani R. An Introduction to Bootstrap. New York, NY: Chapman and Hall; 1993.

    Google Scholar 

  8. Fortier LA, Mohammed HO, Lust G, Nixon AJ. Insulin-like growth factor-I enhances cell-based repair of articular cartilage. J Bone Joint Surg Br. 2002;84:276–288.

    Article  PubMed  CAS  Google Scholar 

  9. Gelse K, von der Mark K, Aigner T, Park J, Schneider H. Articular cartilage repair by gene therapy using growth factor-producing mesenchymal cells. Arthritis Rheum. 2003;48:430–441.

    Article  PubMed  CAS  Google Scholar 

  10. Gillis A, Bashir A, McKeon B, Scheller A, Gray ML, Burstein D. Magnetic resonance imaging of relative glycosaminoglycan distribution in patients with autologous chondrocyte transplants. Invest Radiol. 2001;36:743–748.

    Article  PubMed  CAS  Google Scholar 

  11. Hanemaaijer R, Visser H, Konttinen YT, Koolwijk P, Verheijen JH. A novel and simple immunocapture assay for determination of gelatinase-B (MMP-9) activities in biological fluids: saliva from patients with Sjogren’s syndrome contain increased latent and active gelatinase-B levels. Matrix Biol. 1998;17:657–665.

    Article  PubMed  CAS  Google Scholar 

  12. Kurkijärvi JE, Mattila L, Ojala RO, Vasara AI, Jurvelin JS, Kiviranta I, Nieminen MT. Evaluation of cartilage repair in the distal femur after autologous chondrocyte transplantation using T2 relaxation time and dGEMRIC. Osteoarthritis Cartilage. 2007;15:372–378.

    Article  PubMed  Google Scholar 

  13. Lo MY, Kim HT. Chondrocyte apoptosis induced by collagen degradation: inhibition by caspase inhibitors and IGF-1. J Orthop Res. 2004;22:140–144.

    Article  PubMed  CAS  Google Scholar 

  14. Lohmander LS, Roos H, Dahlberg L, Hoerrner LA, Lark MW. Temporal patterns of stromelysin-1, tissue inhibitor, and proteoglycan fragments in human knee joint fluid after injury to the cruciate ligament or meniscus. J Orthop Res. 1994;12:21–28.

    Article  PubMed  CAS  Google Scholar 

  15. Mankin HJ, Jennings LC, Treadwell BV, Trippel SB. Growth factors and articular cartilage. J Rheumatol Suppl. 1991;27:66–67.

    PubMed  CAS  Google Scholar 

  16. Martel-Pelletier J, Di Battista JA, Lajeunesse D, Pelletier JP. IGF/IGFBP axis in cartilage and bone in osteoarthritis pathogenesis. Inflamm Res. 1998;47:90–100.

    Article  PubMed  CAS  Google Scholar 

  17. Minas T. Autologous chondrocyte implantation for focal chondral defects of the knee. Clin Orthop Relat Res. 2001;391(suppl):S349-S361.

    Article  PubMed  Google Scholar 

  18. Murphy G, Knäuper V, Atkinson S, Butler G, English W, Hutton M, Stracke J, Clark I. Matrix metalloproteinases in arthritic disease. Arthritis Res. 2002;4(suppl 3):S39-S49.

    Article  PubMed  Google Scholar 

  19. Peterson L, Brittberg M, Kiviranta I, Åkerlund EL, Lindahl A. Autologous chondrocyte transplantation: biomechanics and long-term durability. Am J Sports Med. 2002;30:2–12.

    PubMed  Google Scholar 

  20. Peterson L, Minas T, Brittberg M, Nilsson A, Sjögren-Jansson E, Lindahl A. Two- to 9-year outcome after autologous chondrocyte transplantation of the knee. Clin Orthop Relat Res. 2000;374:212–234.

    Article  PubMed  Google Scholar 

  21. Plaas AHK, Sandy JD. Proteoglycan anabolism and catabolism in articular cartilage. In: Kuettner KE, Goldberg VM, eds. Osteoarthritic Disorders. Rosemont, IL: American Academy of Orthopaedic Surgeons; 1995:103–116.

    Google Scholar 

  22. Rahfoth B, Weisser J, Sternkopf F, Aigner T, von der Mark K, Bräuer R. Transplantation of allograft chondrocytes embedded in agarose gel into cartilage defects of rabbits. Osteoarthritis Cartilage. 1998;6:50–65.

    Article  PubMed  CAS  Google Scholar 

  23. Roberts S, Hollander AP, Caterson B, Menage J, Richardson JB. Matrix turnover in human cartilage repair tissue in autologous chondrocyte implantation. Arthritis Rheum. 2001;44:2586–2598.

    Article  PubMed  CAS  Google Scholar 

  24. Roughley PJ, Nguyen Q, Mort JS, Hughes CE, Caterson B. Proteolytic degradation in human articular cartilage: its relationship to stromelysin. Agents Actions Suppl. 1993;39:149–159.

    PubMed  CAS  Google Scholar 

  25. Schneider U, Schlegel U, Bauer S, Siebert CH. Molecular markers in the evaluation of autologous chondrocyte implantation. Arthroscopy. 2003;19:397–403.

    Article  PubMed  Google Scholar 

  26. Schneiderman R, Rosenberg N, Hiss J, Lee P, Liu F, Hintz RL, Maroudas A. Concentration and size distribution of insulin-like growth factor-I in human normal and osteoarthritic synovial fluid and cartilage. Arch Biochem Biophys. 1995;324:173–188.

    Article  PubMed  CAS  Google Scholar 

  27. Smith GD, Taylor J, Almqvist KF, Erggelet C, Knutsen G, Garcia Portabella M, Smith T, Richardson JB. Arthroscopic assessment of cartilage repair: a validation study of 2 scoring systems. Arthroscopy. 2005;21:1462–1467.

    PubMed  Google Scholar 

  28. Smith P, Shuler FD, Georgescu HI, Ghivizzani SC, Johnstone B, Niyibizi C, Robbins PD, Evans CH. Genetic enhancement of matrix synthesis by articular chondrocytes: comparison of different growth factor genes in the presence and absence of interleukin-1. Arthritis Rheum. 2000;43:1156–1164.

    Article  PubMed  CAS  Google Scholar 

  29. Tchetverikov I, Lohmander LS, Verzijl N, Huizinga TW, TeKoppele JM, Hanemaaijer R, DeGroot J. MMP protein and activity levels in synovial fluid from patients with joint injury, inflammatory arthritis, and osteoarthritis. Ann Rheum Dis. 2005;64:694–698.

    Article  PubMed  CAS  Google Scholar 

  30. Tchetverikov I, Ronday HK, Van El B, Kiers GH, Verzijl N, TeKoppele JM, Huizinga TW, DeGroot J, Hanemaaijer R. MMP profile in paired serum and synovial fluid samples of patients with rheumatoid arthritis. Ann Rheum Dis. 2004;63:881–883.

    Article  PubMed  CAS  Google Scholar 

  31. Vasara AI, Nieminen MT, Jurvelin JS, Peterson L, Lindahl A, Kiviranta I. Indentation stiffness of repair tissue after autologous chondrocyte transplantation. Clin Orthop Relat Res. 2005;433:233–242.

    Article  PubMed  Google Scholar 

  32. Walakovits LA, Moore VL, Bhardwaj N, Gallick GS, Lark MW. Detection of stromelysin and collagenase in synovial fluid from patients with rheumatoid arthritis and posttraumatic knee injury. Arthritis Rheum. 1992;35:35–42.

    Article  PubMed  CAS  Google Scholar 

  33. Wang J, Elewaut D, Veys EM, Verbruggen G. Insulin-like growth factor 1-induced interleukin-1 receptor II overrides the activity of interleukin-1 and controls the homeostasis of the extracellular matrix of cartilage. Arthritis Rheum. 2003;48:1281–1291.

    Article  PubMed  CAS  Google Scholar 

  34. Wu JJ, Lark MW, Chun LE, Eyre DR. Sites of stromelysin cleavage in collagen types II, IX, X, and XI of cartilage. J Biol Chem. 1991;266:5625–5628.

    PubMed  CAS  Google Scholar 

  35. Yoshihara Y, Nakamura H, Obata K, Yamada H, Hayakawa T, Fujikawa K, Okada Y. Matrix metalloproteinases and tissue inhibitors of metalloproteinases in synovial fluids from patients with rheumatoid arthritis or osteoarthritis. Ann Rheum Dis. 2000;59:455–461.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

We thank Hannu Kautiainen, BA, from Rheumatism Foundation Hospital, Finland, for statistical analysis and Roeland Haanemaaijer, MD, PhD, TNO Prevention and Health, Leiden, The Netherlands, for expertise in MMP-3 measurements.

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Authors and Affiliations

  1. Department of Orthopaedics and Traumatology, Helsinki University Hospital, Peijas Hospital, Vilkenintie 16 A, 00640, Helsinki, Finland

    Anna I. Vasara MD, PhD

  2. Department of Medicine, Invärtes Medicin, Helsinki University Hospital, Helsinki, Finland

    Yrjö T. Konttinen MD, PhD

  3. ORTON Orthopaedic Hospital of the Invalid Foundation, Helsinki, Finland

    Yrjö T. Konttinen MD, PhD

  4. COXA Hospital for Joint Replacement, Tampere, Finland

    Yrjö T. Konttinen MD, PhD

  5. Institution for Orthopaedics, Göteborg University, Gothenburg, Sweden

    Lars Peterson MD, PhD

  6. Department of Clinical Chemistry and Transfusion Medicine, Institute of Laboratory Medicine, Göteborg University, Gothenburg, Sweden

    Anders Lindahl MD, PhD

  7. Department of Orthopaedics and Traumatology, University of Helsinki, Helsinki, Finland

    Ilkka Kiviranta MD, PhD

  8. Department of Surgery, Jyväskylä Central Hospital, Jyväskylä, Finland

    Ilkka Kiviranta MD, PhD

Authors
  1. Anna I. Vasara MD, PhD
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  2. Yrjö T. Konttinen MD, PhD
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  3. Lars Peterson MD, PhD
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  4. Anders Lindahl MD, PhD
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  5. Ilkka Kiviranta MD, PhD
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Corresponding author

Correspondence to Anna I. Vasara MD, PhD.

Additional information

One or more of the authors (AIV, IK) have received funding from the Instrumentarium Science Foundation and Jyväskylä Central Hospital (Söderholm grant and grant B51).

Each author certifies that his or her institution has approved the human protocol for this investigation, that all investigations were conducted in conformity with ethical principles of research, and that informed consent for participation in the study was obtained.

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Vasara, A.I., Konttinen, Y.T., Peterson, L. et al. Persisting High Levels of Synovial Fluid Markers after Cartilage Repair. Clin Orthop Relat Res 467, 267–272 (2009). https://doi.org/10.1007/s11999-008-0434-x

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  • DOI: https://doi.org/10.1007/s11999-008-0434-x

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