Nitric Oxide Superoxide and Peroxynitrite Modulate Osteoclast Activity

Abstract The gas radical, nitric oxide (NO), is a key signalling molecule in the cardiovascolar, nervous and immune systems. Recently it has been found that it is produced by both the osteoblast and osteoclast and that it has major effects in producing osteoclast detachment and exerting a tonic inhibition of bone resorption. This detaching effect is mediated by a rapid increase in cGMP following calcium-triggered e-NOS activation during normal bone resorption. This effect is not reproduced in vitro by 8-bromo-cGMP but is seen with the newer rapidly permeant 8-pCPT-cGMP. However the inhibition of bone resorption by SIN-1 in vitro is not mediated solely by cGMP but depends on other factors still unidentified. Superoxide anions alone produces both osteoclast detachment and inhibition of resorption. Both of these actions may be mediated at least in part by peroxynitrite which has the same effect as NO alone on osteoclast detachment.