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

Interleukin-6 is elevated in synovial fluid of patients with focal cartilage defects and stimulates cartilage matrix production in an in vitro regeneration model - Download this document for free, or read online. Document in PDF available to download.

Arthritis Research and Therapy

, 14:R262

First Online: 03 December 2012Received: 04 July 2012Revised: 02 November 2012Accepted: 28 November 2012


IntroductionThis 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.

MethodsIL-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.

ResultsSynovial 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.

ConclusionsOur 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.

AbbreviationsACIautologous chondrocyte implantation

ACLanterior cruciate ligament

bFGFbasic fibroblast growth factor

BMIbody mass index

BMP-7bone morphogenetic protein-7

DDR2discoidin domain receptor 2

DMEMDulbecco-s modified Eagle medium

DMMBdimethylmethylene blue


HIF-2αhypoxia-inducible factor-2α



IL-6Rαinterleukin-6 receptor α



PBSphosphate buffered saline

PGE2prostaglandin E2

RArheumatoid arthritis

TIMP-1tissue inhibitor of metalloproteinases 1

TGFβtransforming growth factor β

TNF-αtumor necrosis factor-α

VEGFvascular growth factor

Electronic supplementary materialThe online version of this article doi:10.1186-ar4107 contains supplementary material, which is available to authorized users.

Anika I Tsuchida, Michiel Beekhuizen contributed equally to this work.

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Author: Anika I Tsuchida - Michiel Beekhuizen - Marijn Rutgers - Gerjo JVM van Osch - Joris EJ Bekkers - Arjan GJ Bot - Bernd G


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