D-pinitol inhibits RANKL-induced osteoclastogenesis

Int Immunopharmacol. 2012 Mar;12(3):494-500. doi: 10.1016/j.intimp.2012.01.002. Epub 2012 Jan 23.


Numerous studies have indicated that inflammatory cytokines play a major role in osteoclastogenesis, leading to the bone resorption that is frequently associated with osteoporosis. D-pinitol, a 3-methoxy analogue of D-chiroinositol, was identified as an active principle in soy foods and legumes. Here we found that D-pinitol markedly inhibited the receptor activator of nuclear factor kappa B ligand (RANKL)-induced osteoclastic differentiation from bone marrow stromal cells and RAW264.7 macrophage cells. In addition, D-pinitol also reduced RANKL-induced p38 and JNK phosphorylation. Furthermore, RANKL-mediated increase of IKK, IκBα, and p65 phosphorylation and NF-κB-luciferase activity was inhibited by D-pinitol. However, D-pinitol did not affect the proliferation and differentiation of osteoblasts. In addition, D-pinitol also prevented the bone loss induced by ovariectomy in vivo. Our data suggest that D-pinitol inhibits osteoclastogenesis from bone marrow stromal cells and macrophage cells via attenuated RANKL-induced p38, JNK, and NF-κB activation, which in turn protect bone loss from ovariectomy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Bone Marrow Cells / drug effects
  • Bone Resorption / drug therapy*
  • Bone Resorption / metabolism
  • Cell Differentiation / drug effects
  • Cell Proliferation / drug effects
  • Female
  • Flow Cytometry
  • Growth Inhibitors / pharmacology*
  • Inositol / analogs & derivatives*
  • Inositol / pharmacology
  • MAP Kinase Kinase 4 / biosynthesis
  • MAP Kinase Kinase 4 / genetics
  • Macrophages / drug effects
  • NF-kappa B / metabolism
  • Osteoclasts / drug effects*
  • Osteogenesis / drug effects*
  • Osteoporosis / drug therapy
  • Ovariectomy
  • RANK Ligand / antagonists & inhibitors*
  • RANK Ligand / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Real-Time Polymerase Chain Reaction
  • Stromal Cells / drug effects
  • Transfection
  • p38 Mitogen-Activated Protein Kinases / biosynthesis
  • p38 Mitogen-Activated Protein Kinases / genetics


  • Growth Inhibitors
  • NF-kappa B
  • RANK Ligand
  • pinitol
  • Inositol
  • p38 Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase 4