Differential expression of aggrecanase and matrix metalloproteinase activity in chondrocytes isolated from bovine and porcine articular cartilage.
The release of aggrecan catabolites from cartilage is an early event in the pathogenesis of degenerative joint diseases. The enzymes involved in this process are unknown, controversial, and the subject of intense investigation. In this paper we have utilized a recombinant substrate containing the interglobular domain (IGD) of aggrecan to study specifically aggrecanase versus matrix metalloproteinase (MMP) catabolism in this domain of aggrecan. Our studies have shown that (i) there are species differences in the expression of latent versus active MMP activity on the aggrecan IGD; (ii) interleukin-1alpha exposure induces both aggrecanase and MMP activities, whereas retinoic acid induces only aggrecanase activity and inhibits the MMP activity on the aggrecan IGD; (iii) activators of latent MMP activity (p-aminophenylmercuric acetate and trypsin) significantly reduce aggrecanase activity; (iv) the time course of the appearance of aggrecanase versus the MMP catabolism of aggrecan IGD differs; (v) aggrecanase is a protease with metalloprotease characteristics; however (vi) the physiological (tissue) inhibitors of MMPs show weak inhibition (TIMP-1) or no inhibition (TIMP-2) of aggrecanase activity. Collectively, these studies show that aggrecanase and MMP catabolism of the aggrecan IGD are independent and uncoupled.
Hughes
C E
CE
Connective Tissue Biology Laboratories, Cardiff School of Biosciences, Cardiff University, Cardiff CF1 3US, Wales, United Kingdom. hughesce1@cardiff.ac.uk
Little
C B
CB
Büttner
F H
FH
Bartnik
E
E
Caterson
B
B
D000818:Animals; D002358:Cartilage, Articular / Q000166:cytology / Q000201:enzymology*; D002417:Cattle; D019902:Chondrocytes / Q000201:enzymology*; D017077:Culture Media, Conditioned; D010450:Endopeptidases / Q000096:biosynthesis*; D007375:Interleukin-1 / Q000494:pharmacology; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D011480:Protease Inhibitors / Q000494:pharmacology; D013552:Swine; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000494:pharmacology; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology
D017077:Culture Media, Conditioned; D007375:Interleukin-1; D011480:Protease Inhibitors; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D014212:Tretinoin; D010450:Endopeptidases; D008666:Metalloendopeptidases; C083641:aggrecanase