Vitexin suppresses RANKL-induced osteoclastogenesis and prevents lipopolysaccharide (LPS)-induced osteolysis

J Cell Physiol. 2019 Aug;234(10):17549-17560. doi: 10.1002/jcp.28378. Epub 2019 Feb 21.

Abstract

Osteolytic diseases are characterized by an increase in the number and/or activity of bone-resorbing osteoclasts. Identification of natural compounds that can suppress osteoclast formation and function is crucial for the prevention and treatment of osteolytic diseases. Vitexin, a naturally-derived flavonoid extracted from various medicinal plant species, demonstrates a broad range of pharmacological properties including anticancer and anti-inflammatory effects. Here in this study, we showed that vitexin exerts antiosteoclastogenic effects by directly inhibiting receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast formation and bone resorption in vitro and protected against lipopolysaccharide (LPS)-induced inflammatory osteolysis in vivo. Vitexin suppressed the early activation of ERK and p38 MAPK pathways in response to RANKL thereby attenuating the downstream induction of c-Fos and NFATc1, and abrogating the expression of osteoclast marker genes. Collectively, these results provide evidence for the therapeutic application of vitexin in the treatment of osteoclast-mediated bone lytic diseases.

Keywords: MAPK; osteoclast; osteolysis; therapeutics; vitexin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Animals
  • Apigenin / pharmacology*
  • Bone Remodeling / drug effects
  • Bone Remodeling / physiology
  • Cells, Cultured
  • In Vitro Techniques
  • Lipopolysaccharides / toxicity
  • MAP Kinase Signaling System / drug effects
  • Macrophages / cytology
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Osteoclasts / cytology
  • Osteoclasts / drug effects
  • Osteoclasts / metabolism
  • Osteogenesis / drug effects*
  • Osteogenesis / physiology
  • Osteolysis / chemically induced
  • Osteolysis / metabolism
  • Osteolysis / prevention & control*
  • RANK Ligand / antagonists & inhibitors*
  • RANK Ligand / metabolism

Substances

  • Actins
  • Lipopolysaccharides
  • RANK Ligand
  • Tnfsf11 protein, mouse
  • Apigenin
  • vitexin