title: Xanthohumol modulates the expression of osteoclast-specific genes during osteoclastogenesis in RAW264.7 cells.
abstract: RANKL has been shown to play a critical role in osteoclast formation and bone resorption. Thus, agents that suppress RANKL signaling have a potential to suppress bone loss. In this study, we examined the ability of xanthohumol, a structurally simple prenylated chalcone, to suppress RANKL signaling during osteoclastogenesis in RAW264.7 cells. Xanthohumol markedly inhibited RANKL-induced TRAP activity, multinucleated osteoclasts formation, and resorption-pit formation. In experiments to elucidate its mechanism of action, xanthohumol was found to suppress RANKL-induced expression of TRAF6, GAB2, ERK, c-Src, PI3K, and Akt genes. Moreover, RANKL-induced expressions of c-Fos and NFATc1, which are crucial transcription factors for osteoclastogenesis, were reduced by treatment with xanthohumol. Xanthohumol also inhibited RANKL-induced expression of bone-resorption related osteoclast-specific genes (carbonic anhydrase II, TCIRG, CLCN7, OSTM1, cathepsin K, and MMP-9). These data demonstrate that xanthohumol inhibits osteoclastogenesis by modulating RANKL signaling and may be useful for the prevention of bone-destructive diseases such as osteoporosis, arthritis and periodontitis.
authors.affiliation: Research Institute of Endocrinology, Kyung Hee University Hospital, 1, Hoegi-dong, Dongdaemun-gu, Seoul 130-702, Republic of Korea.
authors.forename: Kwang Sik
authors.initials: KS
authors.lastname: Suh
authors.forename: Sang Youl
authors.initials: SY
authors.lastname: Rhee
authors.forename: Young Seol
authors.initials: YS
authors.lastname: Kim
authors.forename: Young Soon
authors.initials: YS
authors.lastname: Lee
authors.forename: Eun Mi
authors.initials: EM
authors.lastname: Choi
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D024402:Carbonic Anhydrase II / Q000235:genetics; D056657:Cathepsin K / Q000235:genetics; D002460:Cell Line / Q000187:drug effects; D018118:Chloride Channels / Q000235:genetics; D005419:Flavonoids / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D016762:Genes, fos; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D050778:NFATC Transcription Factors / Q000235:genetics; D010010:Osteoclasts / Q000187:drug effects* / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics; D011427:Propiophenones / Q000494:pharmacology*; D053245:RANK Ligand / Q000378:metabolism / Q000494:pharmacology; D048029:TNF Receptor-Associated Factor 6 / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D024402:Carbonic Anhydrase II; D056657:Cathepsin K; D018118:Chloride Channels; D005419:Flavonoids; D020780:Matrix Metalloproteinase 9; D008565:Membrane Proteins; D020928:Mitogen-Activated Protein Kinases; D050778:NFATC Transcription Factors; D019869:Phosphatidylinositol 3-Kinases; D010750:Phosphoproteins; D011427:Propiophenones; D053245:RANK Ligand; D048029:TNF Receptor-Associated Factor 6; C490803:Clcn7 protein, mouse; C490894:Gab2 protein, mouse; C494005:Nfatc1 protein, mouse; C509143:OSTM1 protein, mouse; C505689:Tnfsf11 protein, mouse; C534132:Ctsk protein, mouse; C104536:xanthohumol
keywords: Osteoclastogenesis; RANKL; Signaling pathway; Xanthohumol