Disease-modifying anti-osteoarthritic drugs: current therapies and new prospects around protease inhibition.

Although osteoarthritis is commonly found in the elderly, the pathophysiological mechanisms of this degenerative disease are still poorly understood. Among the many factors leading to cartilage degradation, the proteolytic activity of a panel of enzymes seems to play a major role, leading to the cleavage of collagen and proteoglycans, the two main components of cartilagenous matrix. Aspartic, cysteine, serine and metalloproteases have been detected in or around the osteoarthritic articulation and their enzymatic activity is reviewed here. The cartilage-sparing properties of the respective inhibitors are listed, giving rise to the hypothesis that some of these compounds could be developed as chondroprotective agents.