The biphasic effects of nitric oxide in primary rat osteoblasts are cGMP dependent

Nitric oxide is a gas radical regulating cell, behaviour in the cardiovascu lar, immune, and central nervous systems. It has now been established as an important signalling molecule in bone, However, the effects of this gas ra dical on osteoblastic function are still unclear; in fact, while NO seems t o be involved in anabolic processes mediated by mechanical strain, sex horm ones and fracture healing, it also mediates catabolic processes in response to inflammation. We show here that a slow and moderate release of nitric o xide stimulates the replication of primary rat osteoblasts and alkaline pho sphatase activity, while a rapid release and high concentrations of NO inhi bit proliferation and induce apoptosis. We demonstrate that both the stimul atory and apoptosis-inducing effects of NO on primary osteoblasts are media ted by the second messenger cGMP, since both are abolished by the guanylate cyclase inhibitor ODQ. (C) 2000 Academic Press.