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Human nasal cartilage responds to oncostatin M in combination with interleukin 1 or tumour necrosis factor by the release of collagen fragments via collagenases

T G Morgan¹, A D Rowan¹, S C Dickinson², D Jones¹, A P Hollander², D Deehan³, T E Cawston¹

¹ Musculoskeletal Research Group, School of Clinical Medical Sciences, University of Newcastle, Newcastle-upon-Tyne, UK
² Academic Rheumatology, University of Bristol, Bristol, UK
³ Musculoskeletal Unit (Orthopaedics), Freeman Hospital, Freeman Road, High Heaton, Newcastle-upon-Tyne, UK

Correspondence to:
Dr T E Cawston
Musculoskeletal Research Group, School of Clinical Medical Sciences, University of Newcastle, Newcastle-upon-Tyne NE2 4HH, UK; T.E.Cawston{at}ncl.ac.uk

Background: The synergistic degradation of cartilage by oncostatin M (OSM) in combination with either interleukin 1 (IL1) or tumour necrosis factor (TNF) 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 TNF 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 TNF. HNC responds in the same way as BNC, thus validating the bovine cartilage degradation assay as a model relevant to human disease.

Abbreviations: 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; TNF, tumour necrosis factor

Keywords: collagenase; human cartilage degradation; cytokines; matrix metalloproteinase-1; matrix metalloproteinase-13

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