The prevention of collagen breakdown in bovine nasal cartilage by TIMP, TIMP-2 and a low molecular weight synthetic inhibitor.
Interleukin-1 stimulated bovine nasal cartilage fragments were cultured in the presence and absence of various metalloproteinase inhibitors. Tissue inhibitor of metalloproteinases (TIMP) and tissue inhibitor of metalloproteinases-2 (TIMP-2) completely blocked the release of collagen from the cartilage but were unable to prevent the release of proteoglycan. Similarly, a low molecular weight synthetic inhibitor (BB87) inhibited collagen release in a dose dependent manner, but was unable to inhibit proteoglycan release at the same concentrations. Significantly greater concentrations of inhibitor than those required to block collagen release did, however, block proteoglycan release. These results indicate that the therapeutic use of naturally occurring or synthetic inhibitors may provide a means of modifying the destruction of connective tissue proteins occurring in the arthritides and other connective tissue pathologies.
Ellis
A J
AJ
Rheumatology Research Unit, Addenbrookes Hospital, Cambridge, United Kingdom.
Curry
V A
VA
Powell
E K
EK
Cawston
T E
TE
D000818:Animals; D002356:Cartilage / Q000378:metabolism*; D002417:Cattle; D003094:Collagen / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology; D046508:Culture Techniques; D006023:Glycoproteins / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology; D061965:Matrix Metalloproteinase Inhibitors; D009666:Nose; D010446:Peptide Fragments / Q000494:pharmacology*; D011506:Proteins / Q000494:pharmacology*; D019716:Tissue Inhibitor of Metalloproteinase-2; D019714:Tissue Inhibitor of Metalloproteinases
D006023:Glycoproteins; D007375:Interleukin-1; D061965:Matrix Metalloproteinase Inhibitors; D010446:Peptide Fragments; D011506:Proteins; D019714:Tissue Inhibitor of Metalloproteinases; D019716:Tissue Inhibitor of Metalloproteinase-2; C087431:BB87 collagenase inhibitor; D003094:Collagen