title: Castalagin Exerts Inhibitory Effects on Osteoclastogenesis Through Blocking a Broad Range of Signaling Pathways with Low Cytotoxicity.
abstract: Castalagin is a rare plant polyphenol that is classified as a hydrolyzable tannin. Although it has antioxidant, antitumorigenic, and leishmanicidal effects, the utility of castalagin against bone diseases remain to be elucidated. Here, we investigated the effects of castalagin on the differentiation of osteoclasts (OCLs), multinucleated bone-resorbing cells. After stimulation with receptor activator of nuclear factor kappa-B ligand (RANKL), the formation of OCLs from bone marrow-derived macrophages was significantly inhibited by castalagin even at 1 μM. However, castalagin displayed little cytotoxicity at a higher concentration of 50 μM. The effects of castalagin on intracellular signaling during OCL differentiation showed that castalagin suppresses RANKL-stimulated phosphorylation of major signaling pathways including protein kinase B (Akt), extracellular signal-regulated kinase, Jun N-terminal kinase, p38 mitogen-activated protein kinases, and inhibitor of nuclear factor kappa B alpha. Moreover, following castalagin treatment, the protein levels of nuclear factor of activated T-cells, cytoplasmic 1, a master regulator for OCL differentiation, and NF-κB were decreased. Thus, castalagin exerts inhibitory effects on osteoclastogenesis through blockage of a broad range of signaling pathways, but has low cytotoxicity.
authors: Division of Dental Pharmacology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8588, Japan.
authors: Mayumi
authors: M
authors: Iwatake
authors: Division of Dental Pharmacology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8588, Japan.
authors: Kuniaki
authors: K
authors: Okamoto
authors: Division of Natural Product Chemistry, Nagasaki University Graduate School of Biomedical Sciences, 1-14 Bunkyo, Nagasaki, 852-8521, Japan.
authors: Takashi
authors: T
authors: Tanaka
authors: Division of Dental Pharmacology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8588, Japan.
authors: Takayuki
authors: T
authors: Tsukuba
mesh_terms: D000818:Animals; D001862:Bone Resorption / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D051547:Heme Oxygenase-1 / Q000378:metabolism; D047348:Hydrolyzable Tannins / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism; D050778:NFATC Transcription Factors / Q000378:metabolism; D010010:Osteoclasts / Q000187:drug effects*; D010766:Phosphorylation; D053245:RANK Ligand / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D047348:Hydrolyzable Tannins; D016328:NF-kappa B; D050778:NFATC Transcription Factors; D053245:RANK Ligand; C084709:vescalagin; D051547:Heme Oxygenase-1
keywords: NFATc1; RANKL; castalagin; osteoclasts