Chondroprotection: myth or reality?

Abstract

Osteoarthritis is the most prevalent rheumatic disorder affecting man. It has been estimated to affect approximately 15% of the world's population, making it one of the most common causes of chronic disability (Kellgren and Lawrence, 1957; Kellgren, 1961; Rejholec, 1987). With our aging population, the economic and social costs of osteoarthritis are considerable (Andrews and Ward, 1985). Within recent years research has focused on the changes that take place in cartilage in normal and pathological states and the influence that non-steroidal anti-inflammatory drugs (NSAIDs) may have on the synthesis and degradation of matrix components. The optimal function of diarthroidal joints is dependent on the integrity of articular cartilage, synovial fluid and the synovial membrane. Activated synovial cells as seen in the inflammatory forms of arthritis, such as rheumatoid arthritis or seronegative arthropathies, produce a variety of mediators which can induce cartilage cells to absorb their extracellular matrix in vitro and in vivo. These soluble factors include the interleukin family of proteins (Dingle et al, 1979; Saklatvala, 1981; Wood et al, 1983; van de Loo and van den Berg, 1990) and prostaglandins (Dayer et al, 1976; Mitrovic et al, 1984; Carroll, 1985). Although these and similar factors obviously play a major role in cartilage destruction in inflammatory joint diseases there is still only limited evidence that they are implicated in the pathogenesis of cartilage failure in osteoarthritis (Pelletier and Martel-Pelletier, 1988). While the integrity of cartilage is maintained by the chondrocytes, a major function of the synovial lining type B cells is to synthesize hyaluronic acid, which is the principal non-proteinaceous component of synovial fluid and is essential for the nourishment, protection and lubrication of synovial tissues (Fraser, 1989; Ghosh et al, 1990). The constituents of synovial fluid, as well as the extracellular matrix of cartilage, undergo continuous turnover which may increase during normal physical activity (Engstr6m-Laurent and Hallgren, 1987). In normal joints the biosynthetic capacities of the chondrocytes and the synovial lining cells are sufficient to replenish the levels of proteoglycans and hyaluronic acid which are lost from the tissues by the catabolic processes. However, in the arthritic joint there is a net depletion of proteoglycans from articular cartilage even though chondrocytes are actively engaged in biosynthesis (Mankin et al, 1971; Carney et al, 1984) and