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 i n the pathogenesis of degenerative joint diseases. The enzymes involve d in this process are unknown, controversial, and the subject of inten se investigation. In this paper we have utilized a recombinant substra te containing the interglobular domain (IGD) of aggrecan to study spec ifically 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 acti vity on the aggrecan IGD; (ii) interleukin-1 alpha exposure induces bo th 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 aceta te and trypsin) significantly reduce aggrecanase activity; (iv) the ti me course of the appearance of aggrecanase versus the MMP catabolism o f aggrecan IGD differs; (v) aggrecanase is a protease with metalloprot ease characteristics; however (vi) the physiological (tissue) inhibito rs of MMPs show weak inhibition (TIMP-1) or no inhibition (TIMP-2) of aggrecanase activity. Collectively, these studies show that aggrecanas e and MMP catabolism of the aggrecan IGD are independent and uncoupled .