Nitric oxide (NO), first identified as an endothelium-derived relaxation factor, is now recognized as a regulator of many mammalian cell and tissue functions. It is synthesized via the oxidation of arginine by a family of nitric oxide synthases (NOS) which are either constitutive and calcium-dependent or inducible and calcium-independent. The endogenous production of nitric oxide plays a vital role in regulating physiological processes, e.g., blood vessel tone and neurotransmission, as well as in host defense and immunity. Increasing evidence indicates that nitric oxide also plays a complex role in modulating the inflammatory response.

Our laboratory focuses on the effects of nitric oxide on cellular functions in inflammation, specifically: 1) the inhibitory effects of NO on neutrophil oxidant production which may protect the microvasculature from injury; 2) the modification by NO of key intracellular proteins, including actin, which inhibits their functions; and 3) the production of NO and prostaglandins by cartilage in rheumatoid and osteoarthritis.

Recently, we identified an unusual form of the enzyme which produces NO, i.e., NOS, in the chondrocytes present in osteoarthritic, but not normal, cartilage. This enzyme, which resembles a form of NOS previously identified in brain tissue, spontaneously produces large amounts of NO in cartilage affected by osteoarthritis and may represent a novel target for pharmacological intervention. We are actively engaged in the purification and characterization of this nitric oxide synthase, and we are focusing on the stimuli in osteoarthritic cartilage which provoke its expression.