title: Disruption of NF-κB1 prevents bone loss caused by mechanical unloading.
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.
authors: Division of Molecular Signaling and Biochemistry, Department of Health Improvement, Kyushu Dental University, Fukuoka, Japan.
authors: Hitomi
authors: H
authors: Nakamura
authors: Kazuhiro
authors: K
authors: Aoki
authors: Wataru
authors: W
authors: Masuda
authors: Neil
authors: N
authors: Alles
authors: Kenichi
authors: K
authors: Nagano
authors: Hidefumi
authors: H
authors: Fukushima
authors: Kenji
authors: K
authors: Osawa
authors: Hisataka
authors: H
authors: Yasuda
authors: Ichiro
authors: I
authors: Nakamura
authors: Yuko
authors: Y
authors: Mikuni-Takagaki
authors: Keiichi
authors: K
authors: Ohya
authors: Kenshi
authors: K
authors: Maki
authors: Eijiro
authors: E
authors: Jimi
mesh_terms: D000818:Animals; D001862:Bone Resorption / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005269:Femur / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008817:Mice, Mutant Strains; D052002:NF-kappa B p50 Subunit / Q000235:genetics / Q000378:metabolism*; D010006:Osteoblasts / Q000378:metabolism* / Q000473:pathology; D010010:Osteoclasts / Q000378:metabolism* / Q000473:pathology; D010012:Osteogenesis / Q000235:genetics; D010024:Osteoporosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D053245:RANK Ligand / Q000235:genetics / Q000378:metabolism; D013977:Tibia / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D014893:Weightlessness / Q000009:adverse effects*
chemical_list: D052002:NF-kappa B p50 Subunit; D053245:RANK Ligand; C505689:Tnfsf11 protein, mouse; C073701:Nfkb1 protein, mouse