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-1alpha and oncostatin M (OSM).


METHODS
SSZ was added to bovine nasal explant cultures stimulated to resorb with IL-1alpha 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-1alpha 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-1alpha and OSM.


CONCLUSIONS
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.
Lakey
Rachel L
RL
Musculoskeletal Research Group, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
Cawston
Tim E
TE
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D018501:Antirheumatic Agents / Q000494:pharmacology*; D002358:Cartilage, Articular / Q000187:drug effects / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism*; D017077:Culture Media, Conditioned; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D004353:Drug Evaluation, Preclinical / Q000379:methods; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D051457:Hyaline Cartilage / Q000187:drug effects* / Q000378:metabolism; D053582:Interleukin-1alpha / Q000037:antagonists & inhibitors / Q000494:pharmacology; D045726:Metalloproteases / Q000096:biosynthesis; D055171:Nasal Cartilages / Q000187:drug effects / Q000378:metabolism; D053683:Oncostatin M / Q000037:antagonists & inhibitors / Q000494:pharmacology; D020370:Osteoarthritis, Knee / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism*; D012460:Sulfasalazine / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D018501:Antirheumatic Agents; D017077:Culture Media, Conditioned; D053582:Interleukin-1alpha; D011509:Proteoglycans; D053683:Oncostatin M; D012460:Sulfasalazine; D003094:Collagen; D045726:Metalloproteases