Role of Nitric Oxide and Prostaglandins in Mechanically Induced Bone Formation

We have previously shown that prostaglandins (PG) and nitric oxide (NO) are required in the induction of bone formation by mechanical stimulation. We therefore tested the ability of NO donors, S-nitroso-N-acetyl-D,L-penicillamine (SNAP), and S-nitroso-glutathione (GSNO) to mimic or augment the osteogenic response of bone to a minimal mechanical stimulus. In rats administered vehicle or the vasodilator hydralazine, stimulation of the 8th caudal vertebra increased bone formation. In animals treated with SNAP or GSNO, there was significant potentiation of this osteogenic response. The bone formation rate in nonloaded vertebrae was unaffected by administration of the NO donors. We also found that while inhibition of either PG or NO production at the time of loading caused a partial suppression of c-fos mRNA expression in the loaded vertebrae, administration of indomethacin and NG-monomethyl-L-arginine together markedly suppressed c-fos expression. This suggests that although both PG and NO are required in mechanically induced osteogenesis, they appear to be generated largely independently of each other. Moreover, while exogenous NO potentiates the stimulatory effect of mechanical loading on bone formation, the lack of effect in nonloaded vertebrae suggests that NO is necessary but not sufficient for induction of bone formation. (J Bone Miner Res 1998;13:1039–1044