[Regulation of bone mass for skeletal loading]

Skeletal loading plays an important role in the maintenance of bone mass, bone shape and bone strength. Skeletal unloading, such as during space flight and long-term bed rest, induces bone loss in loaded bones in humans. The mechanotransduction system in bone tissue is not fully elucidated. Our observations demonstrate that generation of nitric oxide through inducible nitric oxide synthase is essential for the stimulation of bone formation upon mechanical reloading, and that disruption of p53 gene in response to 1-week unloading does not result in reductions in bone volume and bone formation. It should be significantly helpful for our understanding of various skeletal disorders to clarify the mechanism underlying regulation of bone mass after skeletal loading and unloading.