title: Tenuigenin inhibits RANKL-induced osteoclastogenesis by down-regulating NF-κB activation and suppresses bone loss in vivo.
abstract: Tenuigenin, a major active component of polygala tenuifolia root, has been used to treat patients with insomnia, dementia, and neurosis. In this study, we aimed to investigate the effects of tenuigenin on osteoclastogenesis and clarify the possible mechanism. We showed that tenuigenin inhibited receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation and bone resorption without cytotoxicity, which was further demonstrated by reduced osteoclast specific gene expression such as TRAP, c-Src, ATP6v0d2, etc. Moreover, the inhibitory effect of tenuigenin was associated with impaired NF-κB activity owing to delayed degradation/regeneration of IkBa and inhibition of p65 nuclear translocation. Consistent with the in vitro results, micro-ct scanning and analysis data showed that tenuigenin suppressed RANKL-induced bone loss in an animal model. Taken together, our data demonstrate that tenuigenin inhibit osteoclast formation and bone resorption both in vitro and in vivo, and comprise a potential therapeutic alternative for osteoclast-related disorders such as osteoporosis and cancer-induced bone destruction.
authors.affiliation: Department of Orthopedic Surgery, The Xiangya Hospital of Central South University, Changsha, Hunan 410008, PR China; Department of Orthopedics, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan 410012, PR China.
authors.forename: Shuo
authors.initials: S
authors.lastname: Yang
authors.affiliation: Department of Orthopedics, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan 410012, PR China.
authors.forename: Xianan
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Orthopedic Surgery, The Xiangya Hospital of Central South University, Changsha, Hunan 410008, PR China.
authors.forename: Liang
authors.initials: L
authors.lastname: Cheng
authors.affiliation: Department of Orthopedics, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan 410012, PR China.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Orthopedic Surgery, The Xiangya Hospital of Central South University, Changsha, Hunan 410008, PR China.
authors.forename: Can
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Orthopedic Surgery, The Xiangya Hospital of Central South University, Changsha, Hunan 410008, PR China. Electronic address: lkh8738@sina.com.
authors.forename: Kanghua
authors.initials: K
authors.lastname: Li
mesh_terms: D000818:Animals; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D001862:Bone Resorption / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism*; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D053245:RANK Ligand / Q000037:antagonists & inhibitors*
chemical_list: D050071:Bone Density Conservation Agents; D004365:Drugs, Chinese Herbal; D016328:NF-kappa B; D053245:RANK Ligand; C505689:Tnfsf11 protein, mouse; C493220:tenuigenin
keywords: NF-κB; Osteoclasts; Osteolysis; RANKL; Tenuigenin