Biochemical mechanisms of articular destruction.

The destruction of articular structures in inflammatory arthritis is a complex process. Both proteolytic degradation of the individual structural proteins that make up the tissues of the joint as well as nonproteolytic processes, such as bone demineralization are involved. Proteinases that can degrade collagen and proteoglycans are present in the various cells that comprise the rheumatoid lesion. Neutrophils contain collagenolytic metalloproteinases (collagenase and gelatinase) as well as potent serine proteinases (elastase and cathepsin G). Synovial cells and chondrocytes secrete metalloproteinases, which are also capable of degrading the extracellular matrix. Evidence would support the concept that the regulatory and counter-regulatory factors that govern the activity of these enzymes are abnormal in inflammatory arthritis, resulting in articular destruction.