Role of eicosanoids in structural degradation in osteoarthritis

Purpose of review Osteoarthritis is characterized mainly by degenerative changes in joint cartilage, ultimately resulting in loss of cartilage, and alterations in the subchondral bone. Osteoarthritis osteoblasts show a number of metabolic alterations that may interfere with normal cell metabolism and signaling, possibly leading to altered extracellular matrix composition. This review examines the role of eicosanoids in this structural degradation. Recent findings Prostaglandins exert diverse modulatory roles in osteoarthritis, with prostaglandin E-2 known to play an important role in inflammation. Prostaglandins and leukotriene B-4 have been shown to regulate proinflammatory cytokine and interstitial collagenase synthesis in human osteoarthritis synovial membrane explants. Human osteoarthritis osteoblasts produce variable levels of prostaglandin E-2 and leukotriene B-4 compared with normal osteoblasts. Prostaglandin E-2 levels can distinguish two types of patients with osteoarthritis: osteoblasts from one group produce low levels of prostaglandin E-2 and interleukin-6, and the other shows an increase in production. In contrast, osteoarthritis osteoblasts that produce high levels of prostaglandin E-2 produce low levels of leukotriene B, and vice versa. This observation could be explained by the selective metabolism of arachidonic acid via the 5-lipoxygenase or cyclooxygenase pathways in osteoarthritis osteoblasts. Summary Prostaglandins play a significant role not only in joint physiology, but also in the pathogenesis of joint disorders. In addition, it has been identified that osteoarthritis subchondral osteoblasts can synthesize leukotriene B-4, indicating a role of leukotrienes in bone remodeling associated with osteoarthritis. A therapeutic intervention that blocks lipoxygenase/cyclooxygenase pathways, thereby inhibiting production of prostaglandins and leukotrienes, may therefore be very attractive for the treatment of osteoarthritis patients.