The Role of Nitric Oxide in Skeletal Simulated Microgravity Response

Prolonged exposure to the space environment leads to bone loss. Using a ground-based model for microgravity (hind-limb unloading), it has been shown in rodents that proliferation and differentiation activity of osteoprogenitors are decreased with exposure to simulated microgravity (Kostenuik et al., 1997). Osteoblast mineralization activity has been shown to increase with nitric oxide supplementation (Afzal et al., 2004; Koyama et al., 2000). I hypothesized that the degenerative effects of microgravity exposure result from chronic changes in nitric oxide regulation in osteoprogenitors, and that supplementation with exogenous nitric oxide following exposure would ameliorate these changes. In 20 C57Bl/6 mice, hind-limb unloading for up to 16 days resulted in degeneration of cancellous tissue in hind-limb bones and a decrease in inducible nitric oxide synthase (iNOS) gene expression in both bone tissue and bone marrow cells. Ex vivo analyses of osteoprogenitor cells, however, showed no changes in differentiation potential or cell count, and supplementation with sodium nitroprusside (SNP) was not able to increase mineralization activity in hind-limb unloaded mice. It is concluded that exogenous nitric oxide supplementation is ineffective as a countermeasure to the effects of simulated microgravity exposure on bone cells