Furosin, an ellagitannin, suppresses RANKL-induced osteoclast differentiation and function through inhibition of MAP kinase activation and actin ring formation

Biochem Biophys Res Commun. 2004 Dec 24;325(4):1472-80. doi: 10.1016/j.bbrc.2004.10.197.


Phenolic compounds including tannins and flavonoids have been implicated in suppression of osteoclast differentiation/function and prevention of bone diseases. However, the effects of hydrolysable tannins on bone metabolism remain to be elucidated. In this study, we found that furosin, a hydrolysable tannin, markedly decreased the differentiation of both murine bone marrow mononuclear cells and Raw264.7 cells into osteoclasts, as revealed by the reduced number of tartrate resistant acid phosphatase (TRAP)-positive multinucleated cells and decreased TRAP activity. Furosin appears to target at the early stage of osteoclastic differentiation while having no cytotoxic effect on osteoclast precursors. Analysis of the inhibitory mechanisms of furosin revealed that it inhibited the receptor activator of nuclear factor-kappaB ligand (RANKL)-induced activation of p38 mitogen-activated protein kinase (p38MAPK) and c-Jun N-terminal kinase (JNK)/activating protein-1 (AP-1). Furthermore, furosin reduced resorption pit formation in osteoclasts, which was accompanied by disruption of the actin rings. Taken together, these results demonstrate that naturally occurring furosin has an inhibitory activity on both osteoclast differentiation and function through mechanisms involving inhibition of the RANKL-induced p38MAPK and JNK/AP-1 activation as well as actin ring formation.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / chemistry
  • Actins / metabolism*
  • Animals
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / drug effects
  • Bone Marrow Cells / physiology
  • Carrier Proteins / pharmacology*
  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology
  • Cell Line
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / pharmacology
  • Hydrolyzable Tannins / pharmacology*
  • MAP Kinase Signaling System / drug effects
  • MAP Kinase Signaling System / physiology
  • Macrophages / cytology
  • Macrophages / drug effects
  • Macrophages / physiology
  • Membrane Glycoproteins / pharmacology*
  • Mice
  • Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • Mitogen-Activated Protein Kinases / metabolism*
  • Osteoclasts / cytology
  • Osteoclasts / drug effects*
  • Osteoclasts / physiology*
  • Protein Conformation
  • RANK Ligand
  • Receptor Activator of Nuclear Factor-kappa B


  • Actins
  • Carrier Proteins
  • Enzyme Inhibitors
  • Hydrolyzable Tannins
  • Membrane Glycoproteins
  • RANK Ligand
  • Receptor Activator of Nuclear Factor-kappa B
  • Tnfrsf11a protein, mouse
  • Tnfsf11 protein, mouse
  • furosin
  • Mitogen-Activated Protein Kinases