Matrix-degrading metalloproteinases and their roles in joint destruction

Abstract Progressive degradation of the extracellular matrix (ECM) of articular cartilage and bone by enhanced activities of proteinases is an essential step for joint destruction in rheumatoid arthritis (RA) and osteoarthritis (OA). Among the proteinases, matrix-degrading metalloproteinases play a key role in joint destruction. Recent studies have indicated that these metalloproteinases comprise members of the matrix metalloproteinase (MMP) and a disintegrin and metalloproteinase (ADAM) gene families. The MMP family is composed of 19 different members and classified into five subgroups of collagenases, gelatinases, stromelysins, membrane-type MMPs, and other MMPs. They have the ability to digest almost all ECM components in human tissues when they act in concert. Their prospective roles in RA and OA joint destruction have been well established. On the other hand, the ADAM family members are classified into ADAM metalloproteinases and catalytically inactive nonproteolytic homologues. The ADAM metalloproteinases contain ADAM with a transmembrane domain (membrane-type ADAM) and ADAM with thrombospondin motifs (ADAMTS). Although members in both groups are known to degrade ECM components, ADAMTS species may be especially important for the aggrecan (cartilage proteoglycan) degradation of articular cartilage in RA and OA, since aggrecanases-1 and -2 are included in this group. This review outlines the characters of the MMP and ADAM gene family members and their roles in joint destruction in RA and OA.