D-pinitol inhibits RANKL-induced osteoclastogenesis.

Abstract

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.

• Authors: Shan-Chi Liu, Show-Mei Chuang, Chih-Hsin Tang
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 12 Issue 3 Pg. 494-500 (Mar 2012) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 22269833 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier B.V. All rights reserved.

Chemical References

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

Topics

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