Mangiferin attenuates osteoclastogenesis, bone resorption, and RANKL-induced activation of NF-κB and ERK

J Cell Biochem. 2011 Jan;112(1):89-97. doi: 10.1002/jcb.22800.


Osteolytic bone diseases such as osteoporosis have a common pathological feature in which osteoclastic bone resorption outstrips bone synthesis. Osteoclast formation and activation are regulated by receptor activator of nuclear factor κB ligand (RANKL). The induction of RANKL-signaling pathways occurs following the interaction of RANKL to its cognate receptor, RANK. This specific binding drives the activation of downstream signaling pathways; which ultimately induce the formation and activation of osteoclasts. In this study, we showed that a natural immunomodulator, mangiferin, inhibits osteoclast formation and bone resorption by attenuating RANKL-induced signaling. Mangiferin diminished the expression of osteoclast marker genes, including cathepsin K, calcitonin receptor, DC-STAMP, and V-ATPase d2. Mechanistic studies revealed that mangiferin inhibits RANKL-induced activation of NF-κB, concomitant with the inhibition of IκB-α degradation, and p65 nuclear translocation. In addition, mangiferin also exhibited an inhibitory effect on RANKL-induced ERK phosphorylation. Collectively, our data demonstrates that mangiferin exhibits anti-resorptive properties, suggesting the potential application of mangiferin for the treatment and prevention of bone diseases involving excessive osteoclastic bone resorption.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Diseases / metabolism
  • Bone Diseases / prevention & control
  • Bone Resorption / metabolism*
  • Cell Differentiation
  • Extracellular Signal-Regulated MAP Kinases / metabolism*
  • Humans
  • Mice
  • Microscopy, Confocal
  • NF-kappa B / metabolism*
  • Osteoclasts / drug effects*
  • Osteoclasts / metabolism
  • RANK Ligand / metabolism*
  • Signal Transduction*
  • Xanthones / pharmacology*
  • eIF-2 Kinase / antagonists & inhibitors
  • eIF-2 Kinase / metabolism


  • NF-kappa B
  • RANK Ligand
  • Xanthones
  • mangiferin
  • eIF-2 Kinase
  • Extracellular Signal-Regulated MAP Kinases