Inhibitory effect of Cudratricusxanthone A on osteoclast differentiation and function

Phytomedicine. 2018 Apr 1:43:86-91. doi: 10.1016/j.phymed.2018.03.060. Epub 2018 Mar 21.

Abstract

Background: Cudratricusxanthone A (CTXA) was isolated from Cudrania tricuspidata and its anti-inflammatory, hepatoprotective, and anti-proliferative activities have previously been studied in vitro. However, effects of CTXA on osteoclast differentiation have not been investigated.

Purpose: In this study, the effect of CTXA from C. tricuspidata on in vitro osteoclastogenesis was studied.

Design/methods: CTXA was isolated from the roots of C. tricuspidata. The effects of CTXA on the RANKL-induced osteoclastogenesis, actin ring formation, and bone resorption were tested by using the RAW 264.7 cells and mouse bone marrow monocytes (BMMs).

Results: The structure of CTXA was identified by comparison with spectral data in the literature. We also checked the effect of CTXA on in vitro osteoclastogenesis. CTXA significantly inhibited the JNK/MAPK signaling pathway without affecting ERK and p38 signaling in RANKL-stimulated RAW 264.7 cells and BMMs. Moreover, it inhibited RANKL-induced expression of c-Fos and NFATc1.

Conclusion: In conclusion, CTXA suppresses osteoclast differentiation by inhibiting RANKL-induced MAPK signaling and attenuates bone resorption by disrupting actin ring formation in mature osteoclasts. These results suggest that CTXA inhibits bone resorption through an inhibitory effect on osteoclast formation and function.

Keywords: Cudratricusxanthone A; MAPK; NFATc1; Osteoclast; Osteoclastogenesis; c-Fos.

MeSH terms

  • Animals
  • Bone Marrow Cells / drug effects
  • Bone Resorption / drug therapy
  • Cell Differentiation / drug effects
  • MAP Kinase Signaling System / drug effects
  • Male
  • Mice
  • Mice, Inbred ICR
  • Moraceae / chemistry
  • Osteoclasts / cytology
  • Osteoclasts / drug effects*
  • Osteoclasts / physiology
  • Plant Roots / chemistry
  • Proto-Oncogene Proteins c-fos / metabolism
  • RANK Ligand / metabolism
  • RANK Ligand / pharmacology
  • RAW 264.7 Cells
  • Signal Transduction / drug effects
  • Xanthones / chemistry*
  • Xanthones / pharmacology*

Substances

  • Proto-Oncogene Proteins c-fos
  • RANK Ligand
  • Xanthones
  • cudratricusxanthone A