Degradation of extracellular matrix in osteoarthritis: 4 fundamental questions.

The destruction of articular cartilage is a hallmark of osteoarthritis. In this process, cartilage fibrillation and eventual erosive lesions result from altered biomechanics generally thought to be preceded by alterations in the cartilage extracellular matrix. The irreversible cartilage changes are, in part, mediated by elevated proteolytic activities of acid and neutral metalloproteases that degrade proteoglycan and Type II collagen. Interestingly, an identical enzyme class is believed to participate in normal turnover of these extracellular matrix constituents. Thus, the control of synovial and cartilage protease activation has become of paramount importance in understanding the role these enzymes play in osteoarthritic pathology.