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 language | English |
|---|---|
| Pages (from-to) | 1457-1467 |
| Number of pages | 11 |
| Journal | Journal of Bone and Mineral Research |
| Volume | 28 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - Jun 1 2013 |
| Externally published | Yes |
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All Science Journal Classification (ASJC) codes
- Endocrinology, Diabetes and Metabolism
- Orthopedics and Sports Medicine
Cite this
Disruption of NF-κB1 prevents bone loss caused by mechanical unloading. / 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.
In: Journal of Bone and Mineral Research, Vol. 28, No. 6, 01.06.2013, p. 1457-1467.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Disruption of NF-κB1 prevents bone loss caused by mechanical unloading
AU - Nakamura, Hitomi
AU - Aoki, Kazuhiro
AU - Masuda, Wataru
AU - Alles, Neil
AU - Nagano, Kenichi
AU - Fukushima, Hidefumi
AU - Osawa, Kenji
AU - Yasuda, Hisataka
AU - Nakamura, Ichiro
AU - Mikuni-Takagaki, Yuko
AU - Ohya, Keiichi
AU - Maki, Kenshi
AU - Jimi, Eijiro
PY - 2013/6/1
Y1 - 2013/6/1
N2 - 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.
AB - 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.
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U2 - 10.1002/jbmr.1866
DO - 10.1002/jbmr.1866
M3 - Article
C2 - 23322687
AN - SCOPUS:84878249993
VL - 28
SP - 1457
EP - 1467
JO - Journal of Bone and Mineral Research
JF - Journal of Bone and Mineral Research
SN - 0884-0431
IS - 6
ER -