Skip to main content
Log in

Correlation of synovial cytokine expression with quality of cells used for autologous chondrocyte implantation in human knees

  • Original Article
  • Published:
European Journal of Orthopaedic Surgery & Traumatology Aims and scope Submit manuscript

Abstract

The cell quality plays a decisive role in autologous chondrocyte implantation (ACI). Aim of the study was the analysis of in vivo interactions between synovial concentrations of cytokines and cell quality used for ACI. Knee lavage fluids of patients undergoing an ACI were examined for total protein content (TPC) and by ELISA for levels of basic fibroblast growth factor (bFGF), insulin-like growth factor 1, bone morphogenetic proteins 2 and 7 (BMP-2 and BMP-7). Cell quality following amplification for ACI was determined by surface expression of CD44, aggrecan, collagen type II and evaluation of cell characteristics. Data of 17 patients were supplemented by epidemiological parameters and clinical scores (IKDC, Lysholm, pain strength, subjective knee function). CD44 expression was positively associated with TPC and bFGF, and negatively linked to BMP-2 levels (p < 0.01). In contrast, expression of collagen type II did not show any statistically significant correlations with synovial protein concentrations. TPC was positively associated with intraarticular bFGF levels and pain strength (p < 0.01), both indicators for osteoarthritis (OA). Correlating with the negative relation of TPC and BMP-2, subjective knee function after 1 year was positively linked to intraarticular BMP-2 concentrations (p < 0.001). Similarly, expression of collagen type II indicated a favorable clinical result reaching statistical significance in case of pain strength (p < 0.01). Initially increased bFGF levels and CD44 expression indicated a worse clinical outcome after 1 year (IKDC, Lysholm Scores, pain strength). Surface expression of CD44 on chondrocytes used for ACI was negatively associated with synovial BMP-2 and positively to TPC and bFGF indicating catabolic synovial conditions. These correlations were also reflected by clinical outcome parameters.

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
Fig. 2

Similar content being viewed by others

References

  1. Jungmann PM, Salzmann GM, Schmal H et al (2012) Autologous chondrocyte implantation for treatment of cartilage defects of the knee: what predicts the need for reintervention? Am J Sports Med 40:58–67. doi:10.1177/0363546511423522

    Article  PubMed  Google Scholar 

  2. Saris DBF, Vanlauwe J, Victor J et al (2009) Treatment of symptomatic cartilage defects of the knee: characterized chondrocyte implantation results in better clinical outcome at 36 months in a randomized trial compared to microfracture. Am J Sports Med 37(Suppl 1):10S–19S. doi:10.1177/0363546509350694

    Article  PubMed  Google Scholar 

  3. Schmal H, Niemeyer P, Südkamp NP et al (2011) Pain perception in knees with circumscribed cartilage lesions is associated with intra-articular IGF-1 expression. Am J Sports Med 39:1989–1996. doi:10.1177/0363546511406851

    Article  PubMed  Google Scholar 

  4. Niemeyer P, Lenz P, Kreuz PC et al (2010) Chondrocyte-seeded type I/III collagen membrane for autologous chondrocyte transplantation: prospective 2-year results in patients with cartilage defects of the knee joint. Arthroscopy 26:1074–1082. doi:10.1016/j.arthro.2009.12.028

    Article  PubMed  Google Scholar 

  5. Niemeyer P, Pestka JM, Salzmann GM et al (2012) Influence of cell quality on clinical outcome after autologous chondrocyte implantation. Am J Sports Med 40:556–561. doi:10.1177/0363546511428879

    Article  PubMed  Google Scholar 

  6. Gerlier L, Lamotte M, Wille M et al (2010) The cost utility of autologous chondrocytes implantation using ChondroCelect® in symptomatic knee cartilage lesions in Belgium. Pharmacoeconomics 28:1129–1146. doi:10.2165/11584920-000000000-00000

    Article  PubMed  Google Scholar 

  7. Honsawek S, Chayanupatkul M, Tanavalee A et al (2009) Relationship of plasma and synovial fluid BMP-7 with disease severity in knee osteoarthritis patients: a pilot study. Int Orthop 33:1171–1175. doi:10.1007/s00264-009-0751-z

    Article  PubMed Central  PubMed  Google Scholar 

  8. Schmal H, Mehlhorn A, Stoffel F et al (2009) In vivo quantification of intraarticular cytokines in knees during natural and surgically induced cartilage repair. Cytotherapy 11:1065–1075. doi:10.3109/14653240903219130

    Article  CAS  PubMed  Google Scholar 

  9. Schmal H, Niemeyer P, Zwingmann J et al (2010) Association between expression of the bone morphogenetic proteins 2 and 7 in the repair of circumscribed cartilage lesions with clinical outcome. BMC Musculoskelet Disord 11:170. doi:10.1186/1471-2474-11-170

    Article  PubMed Central  PubMed  Google Scholar 

  10. Wang L, Verbruggen G, Almqvist KF et al (2001) Flow cytometric analysis of the human articular chondrocyte phenotype in vitro. Osteoarthr Cartil 9:73–84. doi:10.1053/joca.2000.0352

    Article  CAS  PubMed  Google Scholar 

  11. Grogan SP, Barbero A, Diaz-Romero J et al (2007) Identification of markers to characterize and sort human articular chondrocytes with enhanced in vitro chondrogenic capacity. Arthritis Rheum 56:586–595. doi:10.1002/art.22408

    Article  PubMed  Google Scholar 

  12. Brittberg M, Winalski CS (2003) Evaluation of cartilage injuries and repair. J Bone Jt Surg Am 85-A(Suppl 2):58–69

    Google Scholar 

  13. Lysholm J, Gillquist J (1982) Evaluation of knee ligament surgery results with special emphasis on use of a scoring scale. Am J Sports Med 10:150–154

    Article  CAS  PubMed  Google Scholar 

  14. Edwards DJ, Brown JN, Roberts SN, Paterson RS (2000) Long-term results of anterior cruciate ligament reconstruction using ilio-tibial tract and semitendinosis tendon. Knee 7:87–93

    Article  PubMed  Google Scholar 

  15. Niemeyer P, Pestka JM, Kreuz PC et al (2010) Standardized cartilage biopsies from the intercondylar notch for autologous chondrocyte implantation (ACI). Knee Surg Sports Traumatol Arthrosc 18:1122–1127. doi:10.1007/s00167-009-1033-4

    Article  PubMed  Google Scholar 

  16. Pestka JM, Schmal H, Salzmann G et al (2011) In vitro cell quality of articular chondrocytes assigned for autologous implantation in dependence of specific patient characteristics. Arch Orthop Trauma Surg 131:779–789. doi:10.1007/s00402-010-1219-8

    Article  PubMed  Google Scholar 

  17. Häuselmann HJ, Fernandes RJ, Mok SS et al (1994) Phenotypic stability of bovine articular chondrocytes after long-term culture in alginate beads. J Cell Sci 107(Pt 1):17–27

    PubMed  Google Scholar 

  18. Geborek P, Saxne T, Heinegård D, Wollheim FA (1988) Measurement of synovial fluid volume using albumin dilution upon intraarticular saline injection. J Rheumatol 15:91–94

    CAS  PubMed  Google Scholar 

  19. Niemeyer P, Salzmann GM, Hirschmüller A, Südkamp NP (2012) Factors that influence clinical outcome following autologous chondrocyte implantation for cartilage defects of the knee. Z Orthop Unfall 150:83–88. doi:10.1055/s-0030-1270894

    CAS  PubMed  Google Scholar 

  20. Vanlauwe J, Saris DBF, Victor J et al (2011) Five-year outcome of characterized chondrocyte implantation versus microfracture for symptomatic cartilage defects of the knee: early treatment matters. Am J Sports Med 39:2566–2574. doi:10.1177/0363546511422220

    Article  PubMed  Google Scholar 

  21. Saris DBF, Vanlauwe J, Victor J et al (2008) Characterized chondrocyte implantation results in better structural repair when treating symptomatic cartilage defects of the knee in a randomized controlled trial versus microfracture. Am J Sports Med 36:235–246. doi:10.1177/0363546507311095

    Article  PubMed  Google Scholar 

  22. Albrecht C, Schlegel W, Eckl P et al (2009) Alterations in CD44 isoforms and HAS expression in human articular chondrocytes during the de- and re-differentiation processes. Int J Mol Med 23:253–259

    CAS  PubMed  Google Scholar 

  23. Aruffo A, Stamenkovic I, Melnick M et al (1990) CD44 is the principal cell surface receptor for hyaluronate. Cell 61:1303–1313

    Article  CAS  PubMed  Google Scholar 

  24. Barbero A, Grogan SP, Mainil-Varlet P, Martin I (2006) Expansion on specific substrates regulates the phenotype and differentiation capacity of human articular chondrocytes. J Cell Biochem 98:1140–1149. doi:10.1002/jcb.20754

    Article  CAS  PubMed  Google Scholar 

  25. Chow G, Knudson CB, Homandberg G, Knudson W (1995) Increased expression of CD44 in bovine articular chondrocytes by catabolic cellular mediators. J Biol Chem 270:27734–27741

    Article  CAS  PubMed  Google Scholar 

  26. Schmal H, Zwingmann J, Fehrenbach M et al (2007) bFGF influences human articular chondrocyte differentiation. Cytotherapy 9:184–193. doi:10.1080/14653240601182846

    Article  CAS  PubMed  Google Scholar 

  27. Meshcheriakova MG, Trilis IG, Kirillova NV et al (2012) Some biochemical parameters of the synovial liquid for estimation of effectiveness of the treatment of the knee joint osteoarthrosis. Biomed Khim 58:230–236

    CAS  PubMed  Google Scholar 

  28. Yamamoto T, Wakitani S, Imoto K et al (2004) Fibroblast growth factor-2 promotes the repair of partial thickness defects of articular cartilage in immature rabbits but not in mature rabbits. Osteoarthr Cartil 12:636–641. doi:10.1016/j.joca.2004.04.007

    Article  PubMed  Google Scholar 

  29. Kataoka Y, Ariyoshi W, Okinaga T et al (2013) Mechanisms involved in suppression of ADAMTS4 expression in synoviocytes by high molecular weight hyaluronic acid. Biochem Biophys Res Commun 432:580–585. doi:10.1016/j.bbrc.2013.02.043

    Article  CAS  PubMed  Google Scholar 

  30. Kurose R, Ichinohe S, Tajima G et al (2010) Characterization of human synovial fluid cells of 26 patients with osteoarthritis knee for cartilage repair therapy. Int J Rheum Dis 13:68–74. doi:10.1111/j.1756-185X.2009.01456.x

    Article  PubMed  Google Scholar 

  31. Vasara AI, Konttinen YT, Peterson L et al (2009) Persisting high levels of synovial fluid markers after cartilage repair: a pilot study. Clin Orthop Relat Res 467:267–272. doi:10.1007/s11999-008-0434-x

    Article  PubMed Central  PubMed  Google Scholar 

  32. Zhang F-J, Luo W, Gao S-G et al (2013) Expression of CD44 in articular cartilage is associated with disease severity in knee osteoarthritis. Mod Rheumatol. doi:10.1007/s10165-012-0818-3

    Google Scholar 

  33. Cournil-Henrionnet C, Huselstein C, Wang Y et al (2008) Phenotypic analysis of cell surface markers and gene expression of human mesenchymal stem cells and chondrocytes during monolayer expansion. Biorheology 45:513–526

    PubMed  Google Scholar 

  34. Rousche KT, Knudson CB (2002) Temporal expression of CD44 during embryonic chick limb development and modulation of its expression with retinoic acid. Matrix Biol 21:53–62

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The study was funded by the AO Foundation Germany and the Department of Education and Research Germany (01EC1001D).

Conflict of interest

All authors declare to have no financial and personal relationships with other people or organizations that could potentially and inappropriately influence (bias) their work and conclusions.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Hagen Schmal.

Additional information

Trial registration: DRKS00000365.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Schmal, H., Mehlhorn, A.T., Dovi-Akue, D. et al. Correlation of synovial cytokine expression with quality of cells used for autologous chondrocyte implantation in human knees. Eur J Orthop Surg Traumatol 24, 1563–1570 (2014). https://doi.org/10.1007/s00590-014-1436-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00590-014-1436-x

Keywords

Navigation