Human nasal cartilage responds to oncostatin M in combination with interleukin 1 or tumour necrosis factor alpha by the release of collagen fragments via collagenases.
BACKGROUND
The synergistic degradation of cartilage by oncostatin M (OSM) in combination with either interleukin 1 (IL1) or tumour necrosis factor alpha (TNFalpha) has been previously demonstrated using bovine nasal cartilage (BNC).


OBJECTIVE
(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 TNFalpha 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.


CONCLUSIONS
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 TNFalpha. HNC responds in the same way as BNC, thus validating the bovine cartilage degradation assay as a model relevant to human disease.
Musculoskeletal Research Group, School of Clinical Medical Sciences, University of Newcastle, Newcastle-upon-Tyne NE2 4HH, UK. T.E.Cawston@ncl.ac.uk
T G
TG
Morgan
A D
AD
Rowan
S C
SC
Dickinson
D
D
Jones
A P
AP
Hollander
D
D
Deehan
T E
TE
Cawston
D000328:Adult; D000818:Animals; D001681:Biological Assay / Q000379:methods; D015415:Biomarkers / Q000032:analysis; D002417:Cattle; D003094:Collagen / Q000378:metabolism*; D017364:Collagenases / Q000032:analysis / Q000378:metabolism*; D016207:Cytokines / Q000494:pharmacology*; D004357:Drug Synergism; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D020781:Matrix Metalloproteinase 1 / Q000032:analysis; D053509:Matrix Metalloproteinase 13; D008875:Middle Aged; D023421:Models, Animal; D009300:Nasal Septum / Q000187:drug effects* / Q000378:metabolism; D053683:Oncostatin M; D013268:Stimulation, Chemical; D046509:Tissue Culture Techniques; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D015415:Biomarkers; D016207:Cytokines; D007375:Interleukin-1; C508351:OSM protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D014409:Tumor Necrosis Factor-alpha; D053683:Oncostatin M; D003094:Collagen; D017364:Collagenases; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13; D020781:Matrix Metalloproteinase 1