The influence of oxygen tension on the induction of nitric oxide and prostaglandin E2 by mechanical stress in articular cartilage

Objective: 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 (PGE₂) 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 PGE₂ production in articular cartilage in response to mechanical stress. Design: Intermittent mechanical compression (0.05 MPa, 0.5 Hz for 24 h) was applied to full thickness skeletally mature porcine articular cartilage explants at either 20%, 5%, or 1% O₂. NO, PGE₂ and peroxynitrite formation were measured, and the effect of the selective nitric oxide synthase 2 inhibitor 1400 W was tested. Results: Incubating articular cartilage at 5% O₂ significantly increased (P < 0.001) baseline NO production, as compared with 1% or 20% O₂. Peroxynitrite formation was lower at reduced oxygen tension. Mechanical compression significantly increased (P < 0.001) NO production at 20% O₂ but not at 5% or 1% O₂, and significantly increased (P < 0.001) PGE₂ production at 20% O₂ (50 fold) and 5% O₂ (4 fold) but not at 1% O₂. 1400 W blocked mechanically induced NO production and further increased PGE₂ production at 5% O₂ (P < 0.05). Conclusions: Oxygen tension influences the endogenous production of NO and PGE₂ in cartilage and can have a significant effect on the induction of these inflammatory mediators in response to mechanical compression.