title: 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.affiliation: Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan.
authors.forename: Shan-Chi
authors.initials: SC
authors.lastname: Liu
authors.forename: Show-Mei
authors.initials: SM
authors.lastname: Chuang
authors.forename: Chih-Hsin
authors.initials: CH
authors.lastname: Tang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000187:drug effects; D001862:Bone Resorption / Q000188:drug therapy* / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D005434:Flow Cytometry; D006131:Growth Inhibitors / Q000494:pharmacology*; D007294:Inositol / Q000031:analogs & derivatives* / Q000494:pharmacology; D048670:MAP Kinase Kinase 4 / Q000096:biosynthesis / Q000235:genetics; D008264:Macrophages / Q000187:drug effects; D016328:NF-kappa B / Q000378:metabolism; D010010:Osteoclasts / Q000187:drug effects*; D010012:Osteogenesis / Q000187:drug effects*; D010024:Osteoporosis / Q000188:drug therapy; D010052:Ovariectomy; D053245:RANK Ligand / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D017154:Stromal Cells / Q000187:drug effects; D014162:Transfection; D048051:p38 Mitogen-Activated Protein Kinases / Q000096:biosynthesis / Q000235:genetics
chemical_list: D006131:Growth Inhibitors; D016328:NF-kappa B; D053245:RANK Ligand; C021730:pinitol; D007294:Inositol; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4