An aggrecan-degrading activity associated with chondrocyte membranes

The breakdown of aggrecan in cartilage is, in part, mediated by an enzyme n amed aggrecanase that cleaves within the interglobular domain of the molecu le between a glutamic residue and an alanine residue. Although the enzyme c leavage site has been identified, the identity, characteristics and localiz ation of this enzyme remain unclear. We have demonstrated that membranes is olated from stimulated chondrocytes are able to generate aggrecan fragments that are labelled by an antibody that recognizes the new N-terminus formed by aggrecanase activity. It was further shown that the membrane activity w as a metalloproteinase but was not inhibited by the naturally occurring mat rix metalloproteinase (MMP) inhibitors, TIMPs 1 and 2. These results show t hat an aggrecanase activity is associated with the membranes of the chondro cytes and is a metalloproteinase, but might not be a member of the MMP fami ly.