MATRIX METALLOPROTEINASES CLEAVE AT 2 DISTINCT SITES ON HUMAN CARTILAGE LINK PROTEIN

The actions of human recombinant stromelysins-1 and -2, collagenase, g elatinases A and B and matrilysin on neonatal human proteoglycan aggre gates were examined. With the exception of gelatinase B, aggrecan was degraded extensively by most metalloproteinases studied, whereas link protein showed only limited proteolysis. Sequencing studies of modifie d link protein components revealed that stromelysins-1 and -2, gelatin ases A and B and collagenase cleaved specifically between His16 and Il e17, and matrilysin, stromelysin-2 and gelatinase A cleaved between Le u25 and Leu26. Cleavage at the former bond generated a link protein co mponent with the same N-terminus as that isolated from newborn human c artilage. Based on previously determined in situ cleavage sites it is evident that matrix metallo-proteinases are not solely responsible for the accumulation of link protein degradation products in adult human cartilage, indicating that additional proteolytic agents are involved in the normal catabolism of human cartilage matrix.