title: α-Tocotrienol inhibits osteoclastic bone resorption by suppressing RANKL expression and signaling and bone resorbing activity.
abstract: Vitamin E, an essential nutrient with powerful antioxidant activity, is the mixture of two classes of compounds, tocopherols (TPs) and tocotrienols (TTs). Although TTs exhibit better bone protective activity than α-TP, the underlying mechanism is poorly understood. In this study, we investigated whether α-TT and α-TP can modulate osteoclastic bone resorption. We found that α-TT but not α-TP inhibits osteoclastogenesis in coculture of osteoblasts and bone marrow cells induced by either IL-1 or combined treatment with 1α,25(OH)(2) vitamin D(3) and prostaglandin E(2). In accordance with this, only α-TT inhibited receptor activator of NF-κB ligand (RANKL) expression in osteoblasts. In addition, α-TT but not α-TP inhibited RANKL-induced osteoclast differentiation from precursors by suppression of c-Fos expression, possibly through inhibiting ERK and NF-κB activation. This anti-osteoclastogenic effect was reversed when c-Fos or an active form of NFATc1, a critical downstream of c-Fos during osteoclastogenesis, was overexpressed. Furthermore, only α-TT reduced bone resorbing activity of mature osteoclasts without affecting their survival. Overall, our results demonstrate that α-TT but not α-TP has anti-bone resorptive properties by inhibiting osteoclast differentiation and activation, suggesting that α-TT may have therapeutic value for treating and preventing bone diseases characterized by excessive bone destruction.
authors.affiliation: Department of Cell and Developmental Biology, Dental Research Institute, School of Dentistry, Seoul National University, Seoul 110-749, Republic of Korea.
authors.forename: Hyunil
authors.initials: H
authors.lastname: Ha
authors.forename: Jong-Ho
authors.initials: JH
authors.lastname: Lee
authors.forename: Ha-Neui
authors.initials: HN
authors.lastname: Kim
authors.forename: Zang Hee
authors.initials: ZH
authors.lastname: Lee
mesh_terms: D000818:Animals; D001862:Bone Resorption / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects*; D002470:Cell Survival; D002478:Cells, Cultured; D051379:Mice; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects*; D053245:RANK Ligand / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D015398:Signal Transduction / Q000187:drug effects; D024508:Tocotrienols; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D053245:RANK Ligand; D024508:Tocotrienols; D014810:Vitamin E; C082032:tocotrienol, alpha