title: Inhibitory effect of cantharidin on osteoclast differentiation and bone resorption.
abstract: Regulation of receptor activator of nuclear factor kappaB-ligand (RANKL)-induced osteoclast differentiation is of current interest in the development of antiresorptive agents. We identified the inhibitory effects of cantharidin on RANKL-induced differentiation and bone resorptive activities of osteoclasts in macrophage-like RAW264.7 cells. Interestingly, cantharidin significantly inhibited RANKL-induced ERK/MAP kinase activation and protein phosphatase 2A (PP2A) activity. In addition, cantharidin significantly inhibited RANKL-induced mRNA expression of transcription factors and osteoclast-specific genes (especially Fra-2 and cathepsin K, respectively). Although further studies might be required to elucidate the precise mechanism of cantharidin's action on osteoclast differentiation and bone resorptive activities, our results suggested that cantharidin-mediated inactivation of PP2A could prevent RANKLinduced activation of ERK/MAP kinase and transcription factors such as AP-1 and NFATc1, with subsequent inhibition of osteoclast-specific gene expression required for efficient osteoclast differentiation and bone resorption.
authors.affiliation: Laboratory of Chemical Genomics, Korea Research Institute of Chemical Technology, Daejeon, 305-600, Korea.
authors.forename: Myung Hee
authors.initials: MH
authors.lastname: Kim
authors.forename: Ki Shuk
authors.initials: KS
authors.lastname: Shim
authors.forename: Seong Hwan
authors.initials: SH
authors.lastname: Kim
mesh_terms: D000818:Animals; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D001862:Bone Resorption / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D002193:Cantharidin / Q000494:pharmacology*; D056657:Cathepsin K / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects* / Q000235:genetics; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D051921:Fos-Related Antigen-2 / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D051379:Mice; D050778:NFATC Transcription Factors / Q000235:genetics; D010010:Osteoclasts / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D054648:Protein Phosphatase 2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D053245:RANK Ligand / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000235:genetics
chemical_list: D050071:Bone Density Conservation Agents; D004791:Enzyme Inhibitors; D051921:Fos-Related Antigen-2; D050778:NFATC Transcription Factors; C494005:Nfatc1 protein, mouse; D053245:RANK Ligand; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D048049:Extracellular Signal-Regulated MAP Kinases; D054648:Protein Phosphatase 2; D056657:Cathepsin K; C534132:Ctsk protein, mouse; D002193:Cantharidin