Normal and Osteoarthritic Articular Cartilage

Abstract

Summary A self-perpetuating cycle of events occurs in articular cartilage subjected to increased stress that eventually leads to progressive osteoarthritic changes (Fig. 10). Increased stress on cartilage (physical, chemical, or metabolic) sufficient to injure chondrocytes leads to the release of lysosomal and other degradative enzymes. These enzymes degrade the cartilage matrix. Loss of cartilage matrix leads to both degenerative and reparative reactions. Chondrocytes are stimulated both to replicate and to synthesize matrix components as well as to release degradative enzymes. The reparative response is inadequate to compensate for the degradative activity, and continued loss of proteoglycan and loss of collagen architecture lead to loss of the elastic and resilient properties of cartilage. The loss of elasticity leads to further stress on the articular surface causing erosions. As increased stress is transmitted to the subchondral bony plate, microfractures occur and trabeculae increase in thickness and stiffness; thus more force is transmitted back to the overlying articular cartilage. There are a number of sites where this cycle may be interrupted. Current drug therapy is aimed principally at decreasing inflammation, and many drugs act to stabilize the lysosomal membranes and thereby hinder the release of these degradative enzymes. Current research on new drugs has been aimed at specific enzyme inhibitors capable of preventing activation of these endogenous degradative enzymes. Physiotherapeutic aids (e.g., braces and canes) can limit some of the stress on the articular cartilage, and many surgical procedures (e.g., osteotomies) function to limit stress on particular osteoarthritic areas of joints by altering the weight bearing alignment. In our laboratory with Dr. Balazs, we have recently undertaken clinical trials using intraarticular injections of purified hylauronic acid. This has resulted in a return to normal of the reduced viscosity and molecular size of the hyaluronic acid found in arthritic joints. This more nomal fluid may serve to protect the articular surfaces from increased stress. Clinically this drug also appears to decrease pain in these joints. Perhaps the day is not too far off when both the pain and the underlying degenerative disease may be controlled by drugs capable of inhibiting the degenerative response and enhancing the reparative phenomena in articular cartilage.