Fermor B, Christensen S E, Youn I, Cernanec J M, Davies C M, Weinberg J B
Department of Surgery, Division of Orthopaedic Surgery, Duke University Medical Center, Durham, NC 27710, USA.
Eur Cell Mater. 2007 Apr 11;13:56-65; discussion 65. doi: 10.22203/ecm.v013a06.
Molecular oxygen is required for the production of nitric oxide (NO), a pro-inflammatory mediator that is associated with osteoarthritis and rheumatoid arthritis. To date there has been little consideration of the role of oxygen tension in the regulation of nitric oxide production associated with arthritis. Oxygen tension may be particularly relevant to articular cartilage since it is avascular and therefore exists at a reduced oxygen tension. The superficial zone exists at approximately 6% O2, while the deep zone exists at less than 1% O2. Furthermore, oxygen tension can alter matrix synthesis, and the material properties of articular cartilage in vitro. The increase in nitric oxide associated with arthritis can be caused by pro-inflammatory cytokines and mechanical stress. Oxygen tension significantly alters endogenous NO production in articular cartilage, as well as the stimulation of NO in response to both mechanical loading and pro-inflammatory cytokines. Mechanical loading and pro-inflammatory cytokines also increase the production of prostaglandin E2 (PGE2). There is a complex interaction between NO and PGE2, and oxygen tension can alter this interaction. These findings suggest that the relatively low levels of oxygen within the joint may have significant influences on the metabolic activity, and inflammatory response of cartilage as compared to ambient levels. A better understanding of the role of oxygen in the production of inflammatory mediators in response to mechanical loading, or pro-inflammatory cytokines, may aid in the development of strategies for therapeutic intervention in arthritis.
一氧化氮（NO）的产生需要分子氧，NO是一种促炎介质，与骨关节炎和类风湿性关节炎相关。迄今为止，很少有人考虑氧张力在与关节炎相关的一氧化氮产生调节中的作用。氧张力可能与关节软骨特别相关，因为它是无血管的，因此处于较低的氧张力状态。表层区域的氧含量约为6%，而深层区域的氧含量低于1%。此外，氧张力可以改变体外基质合成以及关节软骨的材料特性。与关节炎相关的一氧化氮增加可能由促炎细胞因子和机械应力引起。氧张力显著改变关节软骨中内源性NO的产生，以及对机械负荷和促炎细胞因子刺激的NO产生。机械负荷和促炎细胞因子也会增加前列腺素E2（PGE2）的产生。NO和PGE2之间存在复杂的相互作用，氧张力可以改变这种相互作用。这些发现表明，与环境水平相比，关节内相对较低的氧含量可能对软骨的代谢活性和炎症反应有重大影响。更好地理解氧在响应机械负荷或促炎细胞因子时在炎症介质产生中的作用，可能有助于制定关节炎治疗干预策略。
