Methanol Extract of Croton Pycnanthus Benth. Inhibits Osteoclast Differentiation by Suppressing the MAPK and NF-kappaB Signaling Pathways.
10.11005/jbm.2014.21.4.269
- Author:
Jiyeon LEE
1
;
Hong Hee KIM
Author Information
1. Department of Cell and Developmental Biology, BK21 Program and Dental Research Institute, Seoul National University, Seoul, Korea. hhbkim@snu.ac.kr
- Publication Type:Original Article
- Keywords:
Cell differentiation;
Croton;
Euphorbiaceae;
Osteoclasts;
RANK ligand
- MeSH:
Acid Phosphatase;
Animals;
Antibodies, Phospho-Specific;
Blotting, Western;
Cell Differentiation;
Colony-Stimulating Factors;
Croton*;
Down-Regulation;
Euphorbiaceae;
Humans;
Macrophage Colony-Stimulating Factor;
Macrophages;
Methanol*;
Mice;
NF-kappa B*;
NFATC Transcription Factors;
Osteoclasts*;
Plants;
Protein Kinases;
RANK Ligand;
Real-Time Polymerase Chain Reaction;
Receptor Activator of Nuclear Factor-kappa B;
RNA, Messenger;
T-Lymphocytes
- From:Journal of Bone Metabolism
2014;21(4):269-275
- CountryRepublic of Korea
- Language:English
-
Abstract:
BACKGROUND: Osteoclasts are differentiated from monocytes/macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor-kappa B (NF-kappaB) ligand (RANKL). Croton pycnanthus Benth. (CPB) is a herbal plant that belongs to Euphorbiaceae family. The aim of this study was to investigate the effects of CPB on osteoclastogenesis and RANKL-dependent signaling pathways. METHODS: Methanol extract of CPB was obtained from International Biological Material Research Center. Osteoclast differentiation was achieved by culturing mouse bone marrow-derived macrophages (BMMs) with M-CSF and RANKL. Osteoclast numbers were evaluated by counting multinuclear cells positive for tartrate-resistant acid phosphatase (TRAP). mRNA and protein levels were analyzed by real-time polymerase chain reaction (PCR) and Western blotting, respectively. The activation of signaling molecules were assessed after acute stimulation of cells with high dose of RANKL by Western blotting with phospho-specific antibodies. RESULTS: CPB reduced the generation of TRAP-positive multinucleated cells and the activation of mitogen-activated protein kinase (MAPK) and NF-kappaB signaling pathways. The induction of the expression of c-Fos, nuclear factor-activated T cells c1 (NFATc1) and dendritic cell-specific transmembrane protein (DC-STAMP) by RANKL was also suppressed. CONCLUSIONS: CPB exerts negative effects on osteoclast differentiation in response to the RANKL. The inhibitory mechanism involves the suppression of MAPK and NF-kappaB signaling pathways and subsequently the down-regulation of c-Fos and NFATc1 transcription factors.
