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

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 alpha and oncostatin M (OSM). Methods. SSZ was added to bovine nasal explant cultures stimulated to resorb with IL-1 alpha 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 alpha 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 alpha 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.