title: Arctigenin suppresses receptor activator of nuclear factor κB ligand (RANKL)-mediated osteoclast differentiation in bone marrow-derived macrophages.
abstract: Osteoclasts, multinucleated bone-resorbing cells, are closely associated with bone diseases such as rheumatoid arthritis and osteoporosis. Osteoclasts are derived from hematopoietic precursor cells, and their differentiation is mediated by two cytokines, including macrophage colony stimulating factor and receptor activator of nuclear factor κB ligand (RANKL). Previous studies have shown that arctigenin exhibits an anti-inflammatory effect. However, the effect of arctigenin on osteoclast differentiation is yet to be elucidated. In this study, we found that arctigenin inhibited RANKL-mediated osteoclast differentiation in bone marrow macrophages in a dose-dependent manner and suppressed RANKL-mediated bone resorption. Additionally, the expression of typical marker proteins, such as NFATc1, c-Fos, TRAF6, c-Src, and cathepsin K, were significantly inhibited. Arctigenin inhibited the phosphorylation of Erk1/2, but not p38 and JNK, in a dose-dependent manner. Arctigenin also dramatically suppressed immunoreceptor tyrosine-based activation motif-mediated costimulatory signaling molecules, including Syk and PLCγ2, and Gab2. Notably, arctigenin inhibited the activation of Syk through RANKL stimulation. Furthermore, arctigenin prevented osteoclast differentiation in the calvarial bone of mice following stimulation with lipopolysaccharide. Our results show that arctigenin inhibits osteoclast differentiation in vitro and in vivo. Therefore, arctigenin may be useful for treating rheumatoid arthritis and osteoporosis.
authors.affiliation: Department of Immunology, College of Medicine, Konkuk University, Chungju 380-701, Republic of Korea.
authors.forename: A-Ram
authors.initials: AR
authors.lastname: Kim
authors.forename: Hyuk Soon
authors.initials: HS
authors.lastname: Kim
authors.forename: Jeong Min
authors.initials: JM
authors.lastname: Lee
authors.forename: Jung Ho
authors.initials: JH
authors.lastname: Choi
authors.forename: Se Na
authors.initials: SN
authors.lastname: Kim
authors.forename: Do Kyun
authors.initials: DK
authors.lastname: Kim
authors.forename: Ji Hyung
authors.initials: JH
authors.lastname: Kim
authors.forename: Se Hwan
authors.initials: SH
authors.lastname: Mun
authors.forename: Jie Wan
authors.initials: JW
authors.lastname: Kim
authors.forename: Hyun Soo
authors.initials: HS
authors.lastname: Jeon
authors.forename: Young Mi
authors.initials: YM
authors.lastname: Kim
authors.forename: Wahn Soo
authors.initials: WS
authors.lastname: Choi
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology* / Q000187:drug effects; D001862:Bone Resorption / Q000188:drug therapy; D002454:Cell Differentiation / Q000187:drug effects*; D004789:Enzyme Activation / Q000187:drug effects; D005663:Furans / Q000494:pharmacology* / Q000627:therapeutic use; D005786:Gene Expression Regulation / Q000187:drug effects; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D017705:Lignans / Q000494:pharmacology* / Q000627:therapeutic use; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D053245:RANK Ligand / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D000072377:Syk Kinase
chemical_list: D015415:Biomarkers; D005663:Furans; D047908:Intracellular Signaling Peptides and Proteins; D017705:Lignans; D008070:Lipopolysaccharides; D016328:NF-kappa B; D053245:RANK Ligand; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; C000606897:Syk protein, mouse; C071942:arctigenin