Osteoarthritis (OA) is a degenerative joint disease characterized by destruction of articular cartilage induced by accumulated mechanical stresses to joints. Destruction of the articular cartilage in OA is caused by the combination of (1) increased degradation of ECM (extracellular matrix), (2) decreased production of ECM and (3) chondrocyte death. Members of the MMP (matrix metalloproteinase) and ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) gene families are considered to play key roles in the degradation of cartilage ECM. On the other hand, members of the membrane-type ADAM gene family may be involved in the initiation and progression of OA by regulation of chondrocyte metabolism through shedding of membrane proteins.