Article Text
Abstract
Background: The synergistic degradation of cartilage by oncostatin M (OSM) in combination with either interleukin 1 (IL1) or tumour necrosis factor α (TNFα) has been previously demonstrated using bovine nasal cartilage (BNC).
Objectives: (a) To investigate if human nasal cartilage (HNC) responds in the same way as BNC to these cytokine combinations, particularly in collagen degradation. (b) To compare the response of human nasal and articular cartilages.
Methods: Collagen release was assessed by measuring the hydroxyproline content of culture supernatants and proteoglycan release by the dimethylmethylene blue assay. Matrix metalloproteinase (MMP)-1, MMP-13, and tissue inhibitor of metalloproteinase 1 release were measured by specific enzyme linked immunosorbent assays (ELISAs), and collagenolytic activity was measured by a bioassay using radiolabelled collagen.
Results: OSM in combination with either IL1 or TNFα acted synergistically to induce collagenolysis from HNC, with a maximum of 79% collagen release. This degradation strongly correlated with MMP-1 and MMP-13 levels and collagenolytic activity.
Conclusion: Collagen release from human cartilage is marked and implicates both MMP-1 and MMP-13 in the synergistic degradation of human cartilage by OSM in combination with either IL1 or TNFα. HNC responds in the same way as BNC, thus validating the bovine cartilage degradation assay as a model relevant to human disease.
- BNC, bovine nasal cartilage
- ELISA, enzyme linked immunosorbent assay
- HAC, human articular cartilage
- HNC, human nasal cartilage
- IL1, interleukin 1
- MMP, matrix metalloproteinase
- OA, osteoarthritis
- OSM, oncostatin M
- RA, rheumatoid arthritis
- TIMP, tissue inhibitor of metalloproteinases
- TNFα, tumour necrosis factor α
- collagenase
- human cartilage degradation
- cytokines
- matrix metalloproteinase-1
- matrix metalloproteinase-13
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- BNC, bovine nasal cartilage
- ELISA, enzyme linked immunosorbent assay
- HAC, human articular cartilage
- HNC, human nasal cartilage
- IL1, interleukin 1
- MMP, matrix metalloproteinase
- OA, osteoarthritis
- OSM, oncostatin M
- RA, rheumatoid arthritis
- TIMP, tissue inhibitor of metalloproteinases
- TNFα, tumour necrosis factor α
Footnotes
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Published Online First 23 June 2005
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Conflicting interest: There were no conflicting interests.