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Arctigenin suppresses receptor activator of nuclear factor κB ligand (RANKL)-mediated osteoclast differentiation in bone marrow-derived macrophages.
- Source :
-
European journal of pharmacology [Eur J Pharmacol] 2012 May 05; Vol. 682 (1-3), pp. 29-36. Date of Electronic Publication: 2012 Feb 24. - Publication Year :
- 2012
-
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.<br /> (Copyright © 2012 Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
Biomarkers metabolism
Bone Marrow Cells drug effects
Bone Resorption drug therapy
Enzyme Activation drug effects
Furans therapeutic use
Gene Expression Regulation drug effects
Intracellular Signaling Peptides and Proteins antagonists & inhibitors
Intracellular Signaling Peptides and Proteins metabolism
Lignans therapeutic use
Lipopolysaccharides pharmacology
Male
Mice
Mice, Inbred BALB C
NF-kappa B antagonists & inhibitors
Osteoclasts metabolism
Protein-Tyrosine Kinases antagonists & inhibitors
Protein-Tyrosine Kinases metabolism
Signal Transduction drug effects
Syk Kinase
Bone Marrow Cells cytology
Cell Differentiation drug effects
Furans pharmacology
Lignans pharmacology
Macrophages cytology
Osteoclasts cytology
Osteoclasts drug effects
RANK Ligand metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1879-0712
- Volume :
- 682
- Issue :
- 1-3
- Database :
- MEDLINE
- Journal :
- European journal of pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 22387094
- Full Text :
- https://doi.org/10.1016/j.ejphar.2012.02.026