RESEARCH - Sulfasalazine blocks the release of proteoglycan and collagen from cytokine stimulated cartilage and down-regulates metalloproteinases

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Rheumatology Advance Access originally published online on August 18, 2009

Rheumatology 2009 48(10):1208-1212; doi:10.1093/rheumatology/kep236

Sulfasalazine blocks the release of proteoglycan and collagen from

cytokine stimulated cartilage and down-regulates metalloproteinases

L. Lakey1 and Tim E. Cawston1

1Musculoskeletal Research Group, Institute of Cellular Medicine,

Newcastle University, Newcastle upon Tyne, UK.

Abstract

Objective. To investigate the effect of SSZ on the release of GAG and

collagen fragments from bovine nasal cartilage and MMP and ADAMTS (a

disintegrin and metalloproteinase domain with thrombospondin motifs)

proteinases from human articular chondrocytes (HACs) stimulated with

IL-1 and oncostatin M (OSM).

Methods. SSZ was added to bovine nasal explant cultures stimulated to

resorb with IL-1 and OSM, and the release of GAG and collagen has been

determined. Collagenolytic activity was measured using the

radio-labelled collagen bioassay. HACs were treated with IL-1 and OSM

with and without SSZ, and MMP-1 and -13 and ADAMTS-4 and -5 were

measured for protein and gene expression by ELISA and RT–PCR,

respectively.

Results. SSZ blocked GAG and collagen fragment release from bovine

cartilage, and reduced active and total collagenase activity in a

dose-dependent manner. SSZ transcriptionally blocked MMP-1, -13 and

ADAMTS-4, and reduced the protein levels of MMP-1 and -13 in a

dose-dependent manner following stimulation of HACs with IL-1 and OSM.

Conclusion. This study shows for the first time that SSZ blocks

release of proteoglycan and collagen fragments from resorbing

cartilage and lowers the levels of proteoglycan and collagen-degrading

enzymes. These results indicate that in addition to acting as an

anti-inflammatory agent, SSZ may have a therapeutic role in protecting

cartilage from damage in OA.

http://rheumatology.oxfordjournals.org/cgi/content/abstract/48/10/1208?etoc

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