The effects of static and intermittent compression on nitric oxide production in articular cartilage explants

Nitric oxide (NO) production and NO synthase (NOS) expression are increased in osteoarthritis and rheumatoid arthritis, suggesting that NO may play a role in the destruction of articular cartilage. To test the hypothesis that mechanical stress may increase NO production by chondrocytes, we measured the effects of physiological levels of static and intermittent compression on NOS activity, NO production, and NOS antigen expression by porcine artic ular cartilage explants. Static compression significantly increased NO prod uction at 0.1 MPa stress for 24 h (P < 0.05). Intermittent compression at 0 .5 Hz for 6 h followed by 18 h recovery also increased NO production and NO S activity at 1.0 MPa stress (P < 0.05). Intermittent compression at 0.5 Hz for 24 h at a magnitude of 0.1 or 0.5 MPa caused an increase in NO product ion and NOS activity (P < 0.05). Immunoblot analysis showed stress-induced upregulation of NOS2, but not NOS1 or NOS3. There was no loss in cell viabi lity following any of the loading regimens. Addition of 2 mM 1400 W (a spec ific NOS2 inhibitor) reduced NO production by 51% with no loss of cell viab ility. These findings indicate that NO production by chondrocytes is influe nced by mechanical compression in vitro and suggest that biomechanical fact ors may in part regulate NO production in vivo. (C) 2001 Orthopaedic Resear ch Society. Published by Elsevier Science Ltd. All rights reserved.