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Effect of Anti-c-fms Antibody on Osteoclast Formation and Proliferation of Osteoclast Precursor In Vitro
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Irilin D suppresses RANKL-induced osteoclastogenesis and prevents inflammation-induced bone loss by disrupting the

Minju Gal1, Ha Manh Tuan2, Ju-Hee Park1

  • 1Department of Biochemistry, College of Natural Sciences, Kangwon National University, Chuncheon, Gangwon-Do, 24341, Republic of Korea.

European Journal of Pharmacology
|August 29, 2024
PubMed

Insights

Irilin D, a natural compound, effectively inhibits osteoclast activity and reduces inflammatory bone loss in mice by blocking key signaling pathways. This suggests its potential for treating diseases linked to excessive bone resorption.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Pharmacology

Background:

  • Excessive osteoclast (OC) activity drives bone resorption in inflammatory diseases.
  • Natural compounds offer a promising therapeutic avenue for OC-associated conditions.
  • Irilin D (IRD), a natural isoflavone, has unexplored potential in modulating OC differentiation.

Purpose of the Study:

  • To investigate the effects of Irilin D (IRD) on osteoclast differentiation and function.
  • To explore the therapeutic potential of IRD in inflammatory bone loss models.
  • To elucidate the molecular mechanisms underlying IRD's action on osteoclastogenesis.

Main Methods:

  • In vitro studies on RANKL-induced osteoclast differentiation and resorption.
  • Assessment of IRD's anti-inflammatory effects in LPS-stimulated macrophages.
  • In vivo evaluation of IRD's efficacy in a LPS-induced mouse model of bone loss.
  • Analysis of signaling pathways including MAPKs, NF-κB, c-Fos, and NFATc1.

Main Results:

  • IRD inhibited RANKL-induced OC differentiation, actin ring formation, and bone resorption in vitro without affecting cell viability.
  • IRD did not show anti-inflammatory effects in LPS-stimulated macrophages.
  • IRD significantly reduced LPS-induced inflammatory bone loss in mice by inhibiting osteoclastogenesis.
  • IRD suppressed RANKL-induced activation of MAPKs, NF-κB, c-Fos, and NFATc1, and downregulated NFATc1 target genes.

Conclusions:

  • Irilin D effectively inhibits osteoclast differentiation and function by targeting RANKL-mediated signaling pathways.
  • IRD mitigates inflammatory bone loss in vivo, independent of direct anti-inflammatory effects on macrophages.
  • Irilin D shows potential as a natural therapeutic agent for preventing or treating osteoclast-associated bone diseases.
Keywords:
Inflammatory bone lossIrilin DIsoflavoneNFATc1Osteoclastogenesisc-Fos

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