title: Triptolide, a diterpene, inhibits osteoclastogenesis, induced by RANKL signaling and human cancer cells.
abstract: Most bone-related diseases are characterized by excessive bone resorption by osteoclasts. Receptor activator of nuclear factor-kappa B (NF-κB) ligand (RANKL) has emerged as a major mediator of bone resorption, commonly associated with cancer and chronic inflammatory diseases. Thus inhibitors of RANKL signaling have a potential in preventing bone loss. In the present study, we investigated the ability of triptolide, a diterpenoid isolated from Thunder of God Vine, to inhibit signaling by receptor activator of NF-κB (RANK) and its ligand (RANKL) and to modulate osteoclastogenesis induced by RANKL and human cancer cells. We found that triptolide suppressed RANKL-induced differentiation of precursor cells to osteoclasts, and also inhibited osteoclast formation induced by human breast tumor cells (MDA-MB-231), multiple myeloma cells (U266) and prostate tumor cells (PC-3). Triptolide inhibited RANKL-induced NF-κB activation in osteoclast precursor cells by inhibiting IκBα kinase activation, IκBα phosphorylation, and IκBα degradation. Our results suggest that triptolide effectively inhibits RANKL-induced NF-κB activation and RANKL- and tumor cell-induced osteoclastogenesis. This warrants further study of triptolide as a potential therapy for osteoporosis and cancer-associated bone loss.
authors.affiliation: College of Pharmacy, Keimyung University, Daegu 704-701, Republic of Korea. Electronic address: bdpark@kmu.ac.kr.
authors.forename: Byoungduck
authors.initials: B
authors.lastname: Park
mesh_terms: D000818:Animals; D001862:Bone Resorption / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D004224:Diterpenes / Q000008:administration & dosage; D004852:Epoxy Compounds / Q000008:administration & dosage; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000150:complications / Q000188:drug therapy*; D010010:Osteoclasts / Q000378:metabolism / Q000473:pathology; D010024:Osteoporosis; D010616:Phenanthrenes / Q000008:administration & dosage; D053245:RANK Ligand / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000235:genetics*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D004224:Diterpenes; D004852:Epoxy Compounds; D010616:Phenanthrenes; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C001899:triptolide
keywords: Bone resorption; NF-κB; Osteoclastogenesis; RANKL; Triptolide