Disruption of NF-κB1 prevents bone loss caused by mechanical unloading

Mechanical unloading, such as in a microgravity environment in space or during bed rest (for patients who require prolonged bed rest), leads to a decrease in bone mass because of the suppression of bone formation and the stimulation of bone resorption. To address the challenges presented by a prolonged stay in space and the forthcoming era of a super-aged society, it will be important to prevent the bone loss caused by prolonged mechanical unloading. Nuclear factor B (NF-B) transcription factors are activated by mechanical loading and inflammatory cytokines. Our objective was to elucidate the role of NF-B pathways in bone loss that are caused by mechanical unloading. Eight-week-old wild-type (WT) and NF-B1-deficient mice were randomly assigned to a control or mechanically unloaded with tail suspension group. After 2 weeks, a radiographic analysis indicated a decrease in bone mass in the tibias and femurs of the unloaded WT mice but not in the NF-B1deficient mice. An NF-B1 deficiency suppressed the unloading-induced reduction in bone formation by maintaining the proportion and/or potential of osteoprogenitors or immature osteoblasts, and by suppression of bone resorption through the inhibition of intracellular signaling through the receptor activator of NF-B ligand (RANKL) in osteoclast precursors. Thus, NF-B1 is involved in two aspects of rapid reduction in bone mass that are induced by disuse osteoporosis in space or bed rest.