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

Authors

  • Hitomi Nakamura,

    1. Division of Molecular Signaling and Biochemistry, Department of Health Improvement, Kyushu Dental University, Fukuoka, Japan
    2. Division of Developmental Stomatognathic Function Science, Department of Health Improvement, Kyushu Dental University, Fukuoka, Japan
    Search for more papers by this author
  • Kazuhiro Aoki,

    1. Section of Pharmacology, Department of Bio-Matrix, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan
    Search for more papers by this author
  • Wataru Masuda,

    1. Division of Molecular Signaling and Biochemistry, Department of Health Improvement, Kyushu Dental University, Fukuoka, Japan
    Search for more papers by this author
  • Neil Alles,

    1. Section of Pharmacology, Department of Bio-Matrix, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan
    Search for more papers by this author
  • Kenichi Nagano,

    1. Section of Pharmacology, Department of Bio-Matrix, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan
    Search for more papers by this author
  • Hidefumi Fukushima,

    1. Division of Molecular Signaling and Biochemistry, Department of Health Improvement, Kyushu Dental University, Fukuoka, Japan
    Search for more papers by this author
  • Kenji Osawa,

    1. Division of Molecular Signaling and Biochemistry, Department of Health Improvement, Kyushu Dental University, Fukuoka, Japan
    Search for more papers by this author
  • Hisataka Yasuda,

    1. Planning & Development, Bioindustry Division, Oriental Yeast Co., Ltd., Tokyo, Japan
    Search for more papers by this author
  • Ichiro Nakamura,

    1. Department of Orthopedic Surgery, Mitsui Memorial Hospital, Tokyo, Japan
    Search for more papers by this author
  • Yuko Mikuni-Takagaki,

    1. Division of Biochemistry and Molecular Biology, Department of Functional Biology, Kanagawa Dental College, Yokosuka, Japan
    Search for more papers by this author
  • Keiichi Ohya,

    1. Section of Pharmacology, Department of Bio-Matrix, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan
    Search for more papers by this author
  • Kenshi Maki,

    1. Division of Developmental Stomatognathic Function Science, Department of Health Improvement, Kyushu Dental University, Fukuoka, Japan
    Search for more papers by this author
  • Eijiro Jimi DDSc, PhD

    Corresponding author
    1. Center for Oral Biological Research, Kyushu Dental University, Fukuoka, Japan
    • Division of Molecular Signaling and Biochemistry, Department of Health Improvement, Kyushu Dental University, Fukuoka, Japan
    Search for more papers by this author

Address correspondence to: Division of Molecular Signaling and Biochemistry, Department of Health Improvement, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka 803-8580, Japan. E-mail: ejimi@kyu-dent.ac.jp

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.

Ancillary