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2,5-Dihydroxyacetophenone attenuates RANKL-mediated osteoclastogenesis by affecting the NFATc1 signaling pathway in

Hai-Wei Chen1, Chi-Fen Chen2, Pei-Rong Lee3

  • 1Department of Orthopedic Surgery, Fooyin University Hospital, Pingtung 92849, Taiwan; Department of Medical Laboratory Sciences and Biotechnology, Fooyin University, Kaohsiung 83102, Taiwan.

Bioorganic & Medicinal Chemistry Letters
|November 4, 2024
PubMed

Insights

2,5-dihydroxyacetophenone (DHAP) from Ganoderma bambusicola inhibits osteoclast differentiation and bone resorption. DHAP specifically targets the nuclear factor of activated T-cells cytoplasmic 1 (NFATc1) pathway, offering potential for treating bone loss diseases.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Pharmacology

Background:

  • Osteoclast overactivity drives bone loss in conditions like osteoporosis.
  • Natural compounds offer potential therapeutic strategies for osteolytic diseases.
  • Ganoderma bambusicola contains phenolic compounds with potential bioactivity.

Purpose of the Study:

  • To investigate the anti-osteoclastogenic effects of 2,5-dihydroxyacetophenone (DHAP).
  • To elucidate the molecular mechanisms by which DHAP affects osteoclast differentiation and function.
  • To assess DHAP's impact on RANKL-induced osteoclastogenesis in vitro.

Main Methods:

  • In vitro osteoclast differentiation models using RANKL stimulation.
  • Assessment of osteoclast differentiation markers (actin ring formation, TRAP activity).
  • Analysis of gene and protein expression (NFATc1, Cathepsin K, TRAP).
  • Evaluation of bone resorption activity.
  • Investigation of signaling pathways (NFATc1, AP-1, NF-κB, ROS).

Main Results:

  • DHAP significantly inhibited osteoclast differentiation, actin ring formation, and bone resorption.
  • DHAP suppressed the transcriptional activity of NFATc1 during osteoclastogenesis.
  • Reduced expression of NFATc1, Cathepsin K (Ctsk), and TRAP was observed.
  • DHAP did not affect reactive oxygen species (ROS) production or AP-1 and NF-κB signaling.

Conclusions:

  • DHAP exhibits potent anti-osteoclastogenic activity by inhibiting RANKL-induced osteoclast differentiation and function.
  • The primary mechanism involves the suppression of the NFATc1 signaling pathway.
  • DHAP represents a potential therapeutic candidate for managing osteolytic bone diseases.
Keywords:
2,5-DihydroxyacetophenoneAntiosteoclastogenesisGanoderma bambusicolaNFATc1RANKL

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