Aggrecan fragments are released from human joint cartilage matrix into joint fluid after injury and in osteoarthritis (OA). The temporal patterns of release agree with changes in synthesis and degradation of aggrecan found in experimental animal models of OA. However, we are far from being able to use these molecular fragments to monitor human OA. The structures of the aggrecan fragments remaining in cartilage, and of those being released into joint fluid after cleavage, are consistent with more than one proteolytic agent being active in human joint cartilage after joint injury and in OA.