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

Hitomi Nakamura, Kazuhiro Aoki, Wataru Masuda, Neil Alles, Kenichi Nagano, Hidefumi Fukushima, Kenji Osawa, Hisataka Yasuda, Ichiro Nakamura, Yuko Mikuni-Takagaki, Keiichi Ohya, Kenshi Maki, Eijiro Jimi

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

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 κB (NF-κB) transcription factors are activated by mechanical loading and inflammatory cytokines. Our objective was to elucidate the role of NF-κB pathways in bone loss that are caused by mechanical unloading. Eight-week-old wild-type (WT) and NF-κB1-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-κB1-deficient mice. An NF-κB1 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-κB ligand (RANKL) in osteoclast precursors. Thus, NF-κB1 is involved in two aspects of rapid reduction in bone mass that are induced by disuse osteoporosis in space or bed rest.

Original languageEnglish
Pages (from-to)1457-1467
Number of pages11
JournalJournal of Bone and Mineral Research
Volume28
Issue number6
DOIs
Publication statusPublished - 2013 Jun

Keywords

  • MECHANICAL UNLOADING
  • NF-κB
  • OSTEOBLASTS
  • OSTEOCLASTS

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine

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