Open Access Highly Accessed Research article

Interleukin-6 is elevated in synovial fluid of patients with focal cartilage defects and stimulates cartilage matrix production in an in vitro regeneration model

Anika I Tsuchida1, Michiel Beekhuizen1, Marijn Rutgers1, Gerjo JVM van Osch2, Joris EJ Bekkers1, Arjan GJ Bot1, Bernd Geurts1, Wouter JA Dhert13, Daniel BF Saris14 and Laura B Creemers1*

Author affiliations

1 Department of Orthopaedics, University Medical Center Utrecht, Heidelberglaan 100, Utrecht, 3584 CX, The Netherlands

2 Department of Orthopaedics and Department of Otorhinolaryngology, Erasmus MC, University Medical Center Rotterdam, 's-Gravendijkwal 230, Rotterdam, 3015 CE, The Netherlands

3 Faculty of Veterinary Medicine, University of Utrecht, Yalelaan 1, Utrecht, 3584 CL, The Netherlands

4 Department of Tissue Regeneration, MIRA institute, University of Twente, Drienerlolaan 5, Enschede, 7522 NB, The Netherlands

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Citation and License

Arthritis Research & Therapy 2012, 14:R262  doi:10.1186/ar4107

Published: 3 December 2012

Abstract

Introduction

This study aimed to determine whether, as in osteoarthritis, increased levels of interleukin-6 (IL-6) are present in the synovial fluid of patients with symptomatic cartilage defects and whether this IL-6 affects cartilage regeneration as well as the cartilage in the degenerated knee.

Methods

IL-6 concentrations were determined by ELISA in synovial fluid and in conditioned media of chondrocytes regenerating cartilage. Chondrocytes were obtained from donors with symptomatic cartilage defects, healthy and osteoarthritic donors. The effect of IL-6 on cartilage regeneration and on metabolism of the resident cartilage in the knee was studied by both inhibition of endogenous IL-6 and addition of IL-6, in a regeneration model and in osteoarthritic explants in the presence of synovial fluid, respectively. Readout parameters were DNA and glycosaminoglycan (GAG) content and release. Differences between controls and IL-6 blocked or supplemented samples were determined by univariate analysis of variance using a randomized block design.

Results

Synovial fluid of patients with symptomatic cartilage defects contained more IL-6 than synovial fluid of healthy donors (P = 0.001) and did not differ from osteoarthritic donors. IL-6 production of osteoarthritic chondrocytes during cartilage regeneration was higher than that of healthy and defect chondrocytes (P < 0.001). Adding IL-6 increased GAG production by healthy chondrocytes and decreased GAG release by osteoarthritic chondrocytes (P < 0.05). Inhibition of IL-6 present in osteoarthritic synovial fluid showed a trend towards decreased GAG content of the explants (P = 0.06).

Conclusions

Our results support a modest anabolic role for IL-6 in cartilage matrix production. Targeting multiple cytokines, including IL-6, may be effective in improving cartilage repair in symptomatic cartilage defects and osteoarthritis.