Principal Investigator: Steven B. Abramson, M.D. Professor of Medicine and Pathology NYU School of Medicine. Chairman, Department of Rheumatology and Medicine Hospital for Joint Diseases.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 syntheses (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, specially: 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.
Representative Publications:
Clancy RM, Leszczynska-Piziak J, Amin A, Levartovsky D, and Abramson SB: Nitric oxide stimulates ADP-ribosylation of actin in association with the inhibition of
actin polymerization in human neutrophils. J Leukocyte Biol 58:196-202, 1995.
Amin AR, Di Cesare PE, Vyas P, Attur M, Tzeng E, Billiar TR, Stuchin SA, and Abramson SB: The
expression and regulation of nitric oxide synthase in human osteoarthritis-affected chondrocytes: Evidence for up-regulated neuronal nitric oxide synthase. J Exp Med 182:2097-2102, 1995.
Amin AR, Attur M, Patel RN, Thakker GD, Marshall P, Rediske J, and Abramson SB: Superinduction of cyclooxygenase-2 activity in human osteoarthritis-affected cartilage. J Cli n Invest
99:1231-1237, 1997.
Clancy R, Rediske J, Tang X, Nijher N, Frenkel S, Philips M, and Abramson SB: Outside-In signaling in the chondrocyte: Nitric oxide disrupts fibronectin-induced
assembly of a subplasmalemmal actin/Rho A/ focal adhesion kinase signaling complex. J Clin Invest 100:1789-1796, 1997.
