Regulation of Glucose Transport by Nonsteroidal Anti-inflammatory Drugs

Cartilage destruction in arthritis and OA is linked to aberrant proinflammatory cytokine and growth factor expression in the joint (Chikanza and Fernandes 2000; Malemud et al. 2003). The proinflammatory cytokines TNF-α and IL-β have been found in significantly elevated levels in the synovial fluid of OA joints (Goldring 1999, 2000a; van den Berg 1999). Catabolic pathways are activated by TNF-α and IL-β, which are both upregulated in OA (Malemud et al. 2003). These proinflammatory mediators cause an increase in cartilage matrix degradation through increased MMP and aggrecanase activity in the joint. In addition, TNF-α and IL-β downregulate ECM protein biosynthesis while concomitantly up-regulating matrix MMP gene and protein expression. When MMPs are activated, cartilage ECM degradation ensues apparently because levels of endogenous cartilage MMP inhibitors cannot regulate MMP activity (Malemud et al. 2003).