Eicosanoids, osteoarthritis, and crystal deposition diseases.
OBJECTIVE
Eicosanoids are produced by chondrocytes, synoviocytes, and subchondral osteoblasts within the osteoarthritic joint and are involved in normal joint physiology as well as in the pathogenesis of joint disorders such as osteoarthritis. Calcium-containing crystals are found in most osteoarthritic joints and have been implicated in osteoarthritis. Recent advances in the understanding of the potential role of eicosanoids in the pathogenesis of osteoarthritis and in potential therapeutic targeting of eicosanoid pathways are reviewed.


RESULTS
The ability of interleukin-1beta to upregulate microsomal prostaglandin E2 synthase-1 in synovial fibroblasts and chondrocytes of patients with osteoarthritis has been demonstrated. A potential role for prostaglandin E2 in downregulating interleukin-1beta-induced inflammatory responses has also been described. Basic calcium phosphate crystals can upregulate cyclooxygenase-1 and cocylooxygenase-2 expression, both of which contributed to the observed increase in prostaglandin E2 production in human fibroblasts. Novel potential mechanisms of inhibition of eicosanoid synthesis are also discussed. Last, further evidence of amelioration of osteoarthritis in animal models by the dual 5-lipoxygenase/cyclooxygenase inhibitor licofelone has been reported.


CONCLUSIONS
The inhibition of prostaglandin synthesis has long been a ornerstone of the pharmacologic treatment of osteoarthritis. Nevertheless, prostaglandins may have potentially beneficial as well as deleterious effects in osteoarthritis. In addition, other eicosanoids such as leukotrienes have also been implicated in the pathogenesis of osteoarthritis. Therefore, more selective inhibition of prostaglandin pathways and/or inhibition of leukotriene activity may prove to be effective therapeutic strategies in osteoarthritis.
Molloy
Eamonn S
ES
Department of Clinical Pharmacology, Royal College of Surgeons of Ireland, Dublin, Ireland. emolloy2@rcsi.ie
McCarthy
Geraldine M
GM
D000818:Animals; D002130:Calcium Phosphates / Q000378:metabolism; D015777:Eicosanoids / Q000502:physiology*; D006801:Humans; D010003:Osteoarthritis / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
D002130:Calcium Phosphates; D015777:Eicosanoids; C020243:calcium phosphate