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Nur77 Prevents Osteoporosis by Inhibiting the NF-κB Signalling Pathway and Osteoclast Differentiation

Huanlian Tian1,2, Feng Chen1, Yingfang Wang3

  • 1Department of Gerontology and Geriatrics, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China.

Journal of Cellular and Molecular Medicine
|February 19, 2022
PubMed

Insights

Nuclear receptor 77 (Nur77) inhibits osteoclast differentiation and bone loss by suppressing the NF-κB pathway. Nur77 shows potential for preventing and treating osteoporosis by reducing inflammation.

Area of Science:

  • Molecular Biology
  • Immunology
  • Bone Biology

Background:

  • Inflammation is a key risk factor for osteoporosis.
  • Nuclear receptor 77 (Nur77) has known anti-inflammatory roles, but its function in osteoporosis is uncharacterized.

Purpose of the Study:

  • To investigate the osteoprotective and anti-inflammatory effects of Nur77 in osteoporosis.
  • To elucidate the molecular mechanisms underlying Nur77's role in bone metabolism.

Main Methods:

  • Utilized a knockout mouse model (Nur77 knockout) for in vivo studies.
  • Employed microCT, H&E staining, ELISA, and Western blotting for molecular analysis.
  • Conducted in vitro experiments using RAW264.7 cells to study osteoclast differentiation and inflammatory pathways.

Main Results:

  • Nur77 knockout accelerated femoral bone loss and increased serum levels of hsCRP and IL-6.
  • Knockout mice exhibited elevated expression of NF-κB, IL-6, TNF-α, and osteoclastogenesis factors.
  • Nur77 inhibited osteoclast differentiation by inducing IκB-α and suppressing IKK-β, thereby dampening the NF-κB signaling pathway.

Conclusions:

  • Nur77 suppresses osteoclast differentiation and bone loss by inhibiting the NF-κB signaling pathway.
  • Nur77 demonstrates significant potential as a therapeutic target for preventing and treating osteoporosis.
  • Elevated hsCRP levels are associated with an increased likelihood of osteoporosis in older adults.
Keywords:
NF-κBNur77inflammationosteoclastosteoporosis

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