Disruption of NF-[kappa]B1 prevents bone loss caused by mechanical unloading

• Published in: Journal of bone and mineral research 2013-06, Vol.28 (6), p.1457
• Main Authors: Nakamura, Hitomi, Aoki, Kazuhiro, Masuda, Wataru, Alles, Neil, Nagano, Kenichi, Fukushima, Hidefumi, Osawa, Kenji, Yasuda, Hisataka, Nakamura, Ichiro, Mikuni-Takagaki, Yuko, Ohya, Keiichi, Maki, Kenshi, Jimi, Eijiro
• Format: Article
• Language: English
• Subjects: Osteoporosis; Rodents
• ISSN: 0884-0431; 1523-4681
• DOI: 10.1002/jbmr.1866

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 [kappa]B (NF-[kappa]B) transcription factors are activated by mechanical loading and inflammatory cytokines. Our objective was to elucidate the role of NF-[kappa]B pathways in bone loss that are caused by mechanical unloading. Eight-week-old wild-type (WT) and NF-[kappa]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-[kappa]B1-deficient mice. An NF-[kappa]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-[kappa]B ligand (RANKL) in osteoclast precursors. Thus, NF-[kappa]B1 is involved in two aspects of rapid reduction in bone mass that are induced by disuse osteoporosis in space or bed rest. [PUBLICATION ABSTRACT]