Molloy Eamonn S, McCarthy Geraldine M
Department of Clinical Pharmacology, Royal College of Surgeons of Ireland, Dublin, Ireland.
Curr Opin Rheumatol. 2005 May;17(3):346-50. doi: 10.1097/01.bor.0000155363.61120.c3.
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.
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.
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.
类二十烷酸由骨关节炎关节内的软骨细胞、滑膜细胞和软骨下成骨细胞产生，参与正常关节生理功能以及骨关节炎等关节疾病的发病机制。在大多数骨关节炎关节中发现了含钙晶体，且其与骨关节炎有关。本文综述了在理解类二十烷酸在骨关节炎发病机制中的潜在作用以及类二十烷酸途径潜在治疗靶点方面的最新进展。
已证实白细胞介素-1β可上调骨关节炎患者滑膜成纤维细胞和软骨细胞中的微粒体前列腺素E2合酶-1。还描述了前列腺素E2在下调白细胞介素-1β诱导的炎症反应中的潜在作用。碱性磷酸钙晶体可上调环氧化酶-1和环氧化酶-2的表达，这两者都导致了在人成纤维细胞中观察到的前列腺素E2产生增加。还讨论了抑制类二十烷酸合成的新潜在机制。最后，有报道称双重5-脂氧合酶/环氧化酶抑制剂利考昔对动物模型中骨关节炎的改善有进一步证据。
长期以来，抑制前列腺素合成一直是骨关节炎药物治疗的基石。然而，前列腺素在骨关节炎中可能既有潜在益处也有有害影响。此外，其他类二十烷酸如白三烯也与骨关节炎的发病机制有关。因此，更有选择性地抑制前列腺素途径和/或抑制白三烯活性可能被证明是治疗骨关节炎的有效策略。
