Asiaticoside, a component of Centella asiatica attenuates RANKL-induced osteoclastogenesis via NFATc1 and NF-κB signaling pathways

J Cell Physiol. 2019 Apr;234(4):4267-4276. doi: 10.1002/jcp.27195. Epub 2018 Aug 26.

Abstract

Identification of natural compounds that inhibit osteoclastogenesis will facilitate the development of antiresorptive treatment of osteolytic bone diseases. Asiaticoside is a triterpenoid derivative isolated from Centella asiatica, which exhibits varying biological effects like angiogenesis, anti-inflammation, wound healing, and osteogenic differentiation. However, its role in osteoclastogenesis remains unknown. Here, we show that Asiaticoside can suppress RANKL-induced osteoclast formation and bone resorption in a dose-dependent manner. Asiaticoside attenuated the expression of osteoclast marker genes including Ctsk, Atp6v0d2, Nfatc1, Acp5, and Dc-stamp. Furthermore, Asiaticoside inhibited RANKL-mediated NF-κB and NFATc1 activities, and RANKL-induced calcium oscillation. Collectively, this study demonstrates that Asiaticoside inhibited osteoclast formation and function through attenuating RANKL-induced key signaling pathways, which may indicate that Asiaticoside is a potential antiresorptive agent against osteoclast-related osteolytic bone diseases.

Keywords: NF-κB; NFAT pathway; RANKL; asiaticoside; osteoclast.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium Signaling
  • Centella / chemistry*
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Gene Expression Regulation
  • Macrophages / drug effects*
  • Macrophages / metabolism
  • Mice
  • Mice, Inbred C57BL
  • NF-kappa B / metabolism*
  • NFATC Transcription Factors / genetics
  • NFATC Transcription Factors / metabolism*
  • Osteoclasts / drug effects*
  • Osteoclasts / metabolism
  • Osteogenesis / drug effects*
  • Phosphorylation
  • Proto-Oncogene Proteins c-fos / metabolism
  • RANK Ligand / pharmacology*
  • RAW 264.7 Cells
  • Triterpenes / isolation & purification
  • Triterpenes / pharmacology*

Substances

  • NF-kappa B
  • NFATC Transcription Factors
  • Nfatc1 protein, mouse
  • Proto-Oncogene Proteins c-fos
  • RANK Ligand
  • Triterpenes
  • Extracellular Signal-Regulated MAP Kinases
  • asiaticoside