Fermor Beverley, Weinberg J Brice, Pisetsky David S, Guilak Farshid
Department of Surgery, Division of Orthopaedic Surgery, Box 3093, Duke University Medical Center, NC 27710, USA.
Osteoarthritis Cartilage. 2005 Oct;13(10):935-41. doi: 10.1016/j.joca.2005.05.001. Epub 2005 Jun 22.
Articular cartilage is an avascular tissue that exists at low oxygen tension. Oxygen tension can influence the production of the pro-inflammatory mediators nitric oxide (NO) and prostaglandin E2 (PGE(2)) in cartilage, which are increased in osteoarthritis (OA). The synthesis of these molecules can be stimulated by mechanical stress, which is an important risk factor for OA. The objective of this study was to determine the influence of oxygen tension on the induction of NO and PGE(2) production in articular cartilage in response to mechanical stress.
Intermittent mechanical compression (0.05MPa, 0.5Hz for 24h) was applied to full thickness skeletally mature porcine articular cartilage explants at either 20%, 5%, or 1% O(2). NO, PGE(2) and peroxynitrite formation were measured, and the effect of the selective nitric oxide synthase 2 inhibitor 1400W was tested.
Incubating articular cartilage at 5% O(2) significantly increased (P<0.001) baseline NO production, as compared with 1% or 20% O(2). Peroxynitrite formation was lower at reduced oxygen tension. Mechanical compression significantly increased (P<0.001) NO production at 20% O(2) but not at 5% or 1% O(2), and significantly increased (P<0.001) PGE(2) production at 20% O(2) (50 fold) and 5% O(2) (4 fold) but not at 1% O(2). 1400W blocked mechanically induced NO production and further increased PGE(2) production at 5% O(2) (P<0.05).
Oxygen tension influences the endogenous production of NO and PGE(2) in cartilage and can have a significant effect on the induction of these inflammatory mediators in response to mechanical compression.
关节软骨是一种存在于低氧张力环境下的无血管组织。氧张力可影响软骨中促炎介质一氧化氮（NO）和前列腺素E2（PGE₂）的产生，而在骨关节炎（OA）中这些介质会增加。这些分子的合成可受到机械应力的刺激，机械应力是OA的一个重要危险因素。本研究的目的是确定氧张力对关节软骨在机械应力作用下诱导产生NO和PGE₂的影响。
对全层骨骼成熟的猪关节软骨外植体施加间歇性机械压缩（0.05MPa，0.5Hz，持续24小时），氧浓度分别为20%、5%或1%。测量NO、PGE₂和过氧亚硝酸盐的生成，并测试选择性一氧化氮合酶2抑制剂1400W的作用。
与1%或20%的氧浓度相比，在5%氧浓度下孵育关节软骨显著增加（P<0.001）基线NO生成。在较低氧张力下过氧亚硝酸盐生成较低。机械压缩在20%氧浓度时显著增加（P<0.001）NO生成，但在5%或1%氧浓度时未增加，在20%氧浓度时显著增加（P<0.001）PGE₂生成（50倍），在5%氧浓度时增加（4倍），但在1%氧浓度时未增加。1400W阻断了机械诱导的NO生成，并在5%氧浓度时进一步增加了PGE₂生成（P<0.05）。
氧张力影响软骨中NO和PGE₂的内源性生成，并且对机械压缩诱导这些炎症介质产生有显著影响。
