Decursin inhibits osteoclastogenesis by downregulating NFATc1 and blocking fusion of pre-osteoclasts

Bone. 2015 Dec:81:208-216. doi: 10.1016/j.bone.2015.07.023. Epub 2015 Jul 21.

Abstract

Bone sustains its structure through dynamic interaction between osteoblastic cells and osteoclastic cells. But imbalance may lead to osteoporosis caused by overactivated osteoclast cells that have bone-resorbing function. Recently, herbs have been researched as major sources of medicines in many countries. In vitro and in vivo anti-osteoclastogenic activity of Angelica gigas NAKAI have been reported, but the biological activity of decursin, its major component in osteoclast differentiation is still unknown. Therefore, in this study, we explored whether decursin could affect RANKL-mediated osteoclastogenesis. The results showed that decursin efficiently inhibited RANKL-activated osteoclast differentiation by inhibiting transcriptional and translational expression of NFATc1, a major factor in RANKL-mediated osteoclastogenesis. Furthermore, decursin decreased fusion and migration of pre-osteoclasts by downregulating mRNA expression levels of DC-STAMP and β3 integrin, respectively. In addition, decursin prevents lipopolysaccharide (LPS)-induced bone erosion in vivo. In summary, decursin could prevent osteoclastogenesis and inflammatory bone loss via blockage of NFATc1 activity and fusion and migration of pre-osteoclasts, and it could be developed as a potent phytochemical candidate for treating pathologies of bone diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzopyrans / metabolism*
  • Benzopyrans / pharmacology
  • Butyrates / metabolism*
  • Butyrates / pharmacology
  • Cell Fusion
  • Cell Movement / drug effects
  • Cell Movement / physiology
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Down-Regulation / drug effects
  • Down-Regulation / physiology*
  • Mice
  • Mice, Inbred ICR
  • NFATC Transcription Factors / antagonists & inhibitors*
  • NFATC Transcription Factors / metabolism*
  • Osteoclasts / metabolism*
  • Osteogenesis / drug effects
  • Osteogenesis / physiology*

Substances

  • Benzopyrans
  • Butyrates
  • NFATC Transcription Factors
  • Nfatc1 protein, mouse
  • decursin