Stromelysin 1, neutrophil collagenase, and collagenase 3 do not play major roles in a model of chondrocyte mediated cartilage breakdown.
OBJECTIVE
To determine the collective roles of stromelysin 1, neutrophil collagenase, and collagenase 3 in chondrocyte mediated cartilage proteoglycan and type II collagen degradation in tissue culture model systems.


METHODS
Bovine nasal cartilage explants were cultured with and without recombinant human interleukin 1 alpha (IL-1 alpha), recombinant human tumour necrosis factor alpha, or retinoic acid. Proteoglycan and type II collagen release were determined by colorimetric assay and immunoassay, respectively, in the absence and presence of matrixin inhibitors. Potential toxic effects of the inhibitors were assessed by measuring rates of glycolysis.


RESULTS
Loss of proteoglycan and type II collagen from nasal cartilage was inhibited by batimastat, a broad spectrum matrixin inhibitor. BB-3437, a selective inhibitor of stromelysin, neutrophil collagenase, and collagenase 3, at the concentrations used in this study, showed a weak but dose dependent inhibitory effect on the IL-1 stimulated degradation of type II collagen, but had virtually no effect on proteoglycan breakdown. Neither inhibitor affected rates of glycolysis.


CONCLUSIONS
Stromelysin 1, neutrophil collagenase, and collagenase 3 are unlikely to contribute to chondrocyte mediated proteoglycan degradation in our model system. The modest effect of a selective inhibitor of these enzymes on IL-1 stimulated collagen breakdown suggests a minor role for one or more of these proteinases; potent inhibition by an inhibitor of interstitial collagenase and the gelatinases suggests that these enzymes play a major role in IL-1 stimulated, chondrocyte mediated type II collagen breakdown from nasal cartilage.
Kozaci
L D
LD
Section of Human Metabolism and Clinical Biochemistry, University of Sheffield Medical School, UK.
Brown
C J
CJ
Adcocks
C
C
Galloway
A
A
Hollander
A P
AP
Buttle
D J
DJ
D000577:Amides / Q000494:pharmacology; D000818:Animals; D002356:Cartilage / Q000187:drug effects / Q000378:metabolism*; D002417:Cattle; D019902:Chondrocytes / Q000502:physiology*; D003094:Collagen / Q000378:metabolism; D017364:Collagenases / Q000502:physiology; D046508:Culture Techniques; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D019278:Matrix Metalloproteinase 3 / Q000502:physiology; D061965:Matrix Metalloproteinase Inhibitors; D008666:Metalloendopeptidases / Q000502:physiology*; D009300:Nasal Septum / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology
D000577:Amides; C118547:BB 3437; D004791:Enzyme Inhibitors; D007375:Interleukin-1; D061965:Matrix Metalloproteinase Inhibitors; D011509:Proteoglycans; D011994:Recombinant Proteins; D003094:Collagen; D017364:Collagenases; D008666:Metalloendopeptidases; D019278:Matrix Metalloproteinase 3