The influence of tissue cross-talking on OA progression: role of nonsteroidal antiinflammatory drugs

Osteoarthritis is increasingly recognized as a complex illness in which interrelationships between the different tissues of the joint are important. We are still some way from a complete understanding of the pathophysiologic and temporal relationships between bone, synovial tissue and cartilage. Recent evidence points to a significant role for cytokines and growth factors in osteoarthritis that leads to a preponderance of catabolic processes in the joint. In-vitroculture of human cartilage has been used as a model to measure the effects of drugs used in the treatment of osteoarthritis on anabolic and catabolic processes. On this basis, the nonsteroidal antiinflammatory drugs can be categorized into one of three classes depending on whether they are inhibitory (e.g., indomethacin and naproxen), neutral (e.g., diclofenac, aspirin and piroxicam) or stimulatory (e.g., aceclofenac, tenidap and tolmetin) of glycosaminoglycan synthesis in chondrocytes. The marked differences between these nonsteroidal antiinflammatory drugs suggest that a mechanism other than cyclooxygenase inhibition is involved in their effects on glycosaminoglycan synthesis. Inhibition of IL-1β and the stimulation of growth factors are suggested as possible mechanisms. Although the significance of these properties of nonsteroidal antiinflammatory drugs awaits confirmation inin-vivoand clinical situations, they do provide the clinician with a new parameter with which to choose therapy in osteoarthritis.