Seminars in Arthritis and Rheumatism

Objectives: Structure-modifying osteoarthritis (OA) drugs (SMOADs) may be defined as agents that reverse, retard, or stabilize the underlying pathology of OA, thereby providing symptomatic relief in the long-term. The objective of this review was to evaluate the literature on sodium pentosan polysulfate (NaPPS) and calcium pentosan polysulfate (CaPPS), with respect to the pathobiology of OA to ascertain whether these agents should be classified as SMOADs. Methods: Published studies on NaPPS and CaPPS were selected on the basis of their relevance to the known pathobiology of OA, which also was reviewed. Results: Both NaPPS and CaPPS exhibit a wide range of pharmacological activities. Of significance was the ability of these agents to support chondrocyte anabolic activities and attenuate catabolic events responsible for loss of components of the cartilage extracellular matrix in OA joints. Although some of the anti-catabolic activities may be mediated through direct enzyme inhibition, NaPPS and CaPPS also have been shown to enter chondrocytes and bind to promoter proteins and alter gene expression of matrix metalloproteinases and possibly other mediators. In rat models of arthritis, NaPPS and CaPPS reduced joint swelling and inflammatory mediator levels in pouch fluids. Moreover, synoviocyte biosynthesis of high-molecular-weight hyaluronan, which is diminished in OA, was normalized when these cells were incubated with NaPPS and CaPPS or after intraarticular injection of NaPPS into arthritic joints. In rabbit, canine, and ovine models of OA, NaPPS and CaPPS preserved cartilage integrity, proteoglycan synthesis, and reduced matrix metalloproteinase activity. NaPPS and CaPPS stimulated the release of tissue plasminogen activator (t-PA), superoxide dismutase, and lipases from vascular endothelium while concomitantly decreasing plasma levels of the endogenous plasminogen activator inhibitor PAl-l. The net thrombolytic and lipolytic effects exhibited by NaPPS and CaPPS may serve to improve blood flow through subchondral capillaries of OA joints and improve bone cell nutrition. In geriatric OA dogs,