Laufer Stefan
Institute of Pharmacy, University of Tuebingen, Germany.
Curr Opin Rheumatol. 2003 Sep;15(5):623-7. doi: 10.1097/00002281-200309000-00017.
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.
Prostaglandins exert diverse modulatory roles in osteoarthritis, with prostaglandin E2 known to play an important role in inflammation. Prostaglandins and leukotriene B4 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 E2 and leukotriene B4 compared with normal osteoblasts. Prostaglandin E2 levels can distinguish two types of patients with osteoarthritis: osteoblasts from one group produce low levels of prostaglandin E2 and interleukin-6, and the other shows an increase in production. In contrast, osteoarthritis osteoblasts that produce high levels of prostaglandin E2 produce low levels of leukotriene B4 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.
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 B4, 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.
骨关节炎主要特征为关节软骨发生退行性改变，最终导致软骨丢失以及软骨下骨改变。骨关节炎成骨细胞表现出多种代谢改变，这些改变可能干扰正常细胞代谢和信号传导，进而可能导致细胞外基质组成改变。本综述探讨类花生酸在这种结构破坏中的作用。
前列腺素在骨关节炎中发挥多种调节作用，已知前列腺素E2在炎症中起重要作用。前列腺素和白三烯B4已被证明可调节人骨关节炎滑膜外植体中促炎细胞因子和间质胶原酶的合成。与正常成骨细胞相比，人骨关节炎成骨细胞产生不同水平的前列腺素E2和白三烯B4。前列腺素E2水平可区分两类骨关节炎患者：一组成骨细胞产生低水平的前列腺素E2和白细胞介素-6，另一组则产量增加。相反，产生高水平前列腺素E2的骨关节炎成骨细胞产生低水平的白三烯B4，反之亦然。这一观察结果可以通过骨关节炎成骨细胞中花生四烯酸经5-脂氧合酶或环氧化酶途径的选择性代谢来解释。
前列腺素不仅在关节生理中起重要作用，在关节疾病的发病机制中也起重要作用。此外，已确定骨关节炎软骨下成骨细胞可合成白三烯B4，表明白三烯在与骨关节炎相关的骨重塑中起作用。因此，一种阻断脂氧合酶/环氧化酶途径从而抑制前列腺素和白三烯产生的治疗干预措施，可能对治疗骨关节炎患者非常有吸引力。
