Methanol Extract of Croton Pycnanthus Benth. Inhibits Osteoclast Differentiation by Suppressing the MAPK and NF-κB Signaling Pathways
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Background: Osteoclasts are differentiated from monocytes/macrophage colony-stim-ulating factor (M-CSF) and receptor activator of nuclear factor-kappa B (NF-κB) ligand(RANKL). Croton pycnanthus Benth. (CPB) is a herbal plant that belongs to Euphorbiaceaefamily. The aim of this study was to investigate the effects of CPB on osteoclastogenesisand RANKL-dependent signaling pathways. Methods: Methanol extract of CPB was ob-tained from International Biological Material Research Center. Osteoclast differentiationwas achieved by culturing mouse bone marrow-derived macrophages (BMMs) with M-CSF and RANKL. Osteoclast numbers were evaluated by counting multinuclear cells pos-itive for tartrate-resistant acid phosphatase (TRAP). mRNA and protein levels were ana-lyzed by real-time polymerase chain reaction (PCR) and Western blotting, respectively. The activation of signaling molecules were assessed after acute stimulation of cells withhigh dose of RANKL by Western blotting with phospho-specific antibodies. Results: CPBreduced the generation of TRAP-positive multinucleated cells and the activation of mi-togen-activated protein kinase (MAPK) and NF-κB signaling pathways. The induction ofthe expression of c-Fos, nuclear factor-activated T cells c1 (NFATc1) and dendritic cell-spe-cific transmembrane protein (DC-STAMP) by RANKL was also suppressed. Conclusions:CPB exerts negative effects on osteoclast differentiation in response to the RANKL. Theinhibitory mechanism involves the suppression of MAPK and NF-κB signaling pathwaysand subsequently the down-regulation of c-Fos and NFATc1 transcription factors.
Abstract
Background: Osteoclasts are differentiated from monocytes/macrophage colony-stim-ulating factor (M-CSF) and receptor activator of nuclear factor-kappa B (NF-κB) ligand(RANKL). Croton pycnanthus Benth. (CPB) is a herbal plant that belongs to Euphorbiaceaefamily. The aim of this study was to investigate the effects of CPB on osteoclastogenesisand RANKL-dependent signaling pathways. Methods: Methanol extract of CPB was ob-tained from International Biological Material Research Center. Osteoclast differentiationwas achieved by culturing mouse bone marrow-derived macrophages (BMMs) with M-CSF and RANKL. Osteoclast numbers were evaluated by counting multinuclear cells pos-itive for tartrate-resistant acid phosphatase (TRAP). mRNA and protein levels were ana-lyzed by real-time polymerase chain reaction (PCR) and Western blotting, respectively. The activation of signaling molecules were assessed after acute stimulation of cells withhigh dose of RANKL by Western blotting with phospho-specific antibodies. Results: CPBreduced the generation of TRAP-positive multinucleated cells and the activation of mi-togen-activated protein kinase (MAPK) and NF-κB signaling pathways. The induction ofthe expression of c-Fos, nuclear factor-activated T cells c1 (NFATc1) and dendritic cell-spe-cific transmembrane protein (DC-STAMP) by RANKL was also suppressed. Conclusions:CPB exerts negative effects on osteoclast differentiation in response to the RANKL. Theinhibitory mechanism involves the suppression of MAPK and NF-κB signaling pathwaysand subsequently the down-regulation of c-Fos and NFATc1 transcription factors.
참고문헌 (23)
- Lacey DL., "Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation", Cell., 93, pp.165~176 (1998)
- Fuller K., "TRANCE is necessary and sufficient for osteoblast-mediated activation of bone resorption in osteoclasts", J Exp Med., 188, pp.997~1001 (1998)
- Miyamoto T., "Bifurcation of osteoclasts and dendritic cells from common progenitors", Blood., 98, pp.2544~2554 (2001)
- Takayanagi H., "Induction and activation of the transcription factor NFATc1 (NFAT2) integrate RANKL signaling in terminal differentiation of osteoclasts", Dev Cell., 3, pp.889~901 (2002)
- Wagner EF., "Fos", AP-1 proteins in bone and the immune system, 2005, pp.208, 126~140
- Aliprantis AO., "NFATc1 in mice represses osteoprotegerin during osteoclastogenesis and dissociates systemic osteopenia from inflammation in cherubism", J Clin Invest., 118, pp.3775~3789 (2008)
- Asagiri M., "Autoamplification of NFATc1 expression determines its essential role in bone homeostasis", J Exp Med., 202, pp.1261~1269 (2005)
- Lee ZH., "Signal transduction by receptor activator of nuclear factor kappa B in osteoclasts", Biochem Biophys Res Commun., 305, pp.211~214 (2003)
- Takayanagi H., "Osteoimmunology: shared mechanisms and crosstalk between the immune and bone systems", Nat Rev Immunol., 7, pp.262~304 (2007)
- Yagi M., "DC-STAMP is essential for cell-cell fusion in osteoclasts and foreign body giant cells", J Exp Med., 202, pp.345~351 (2005)
- Dougall WC., "RANK is essential for osteoclast and lymph node development", Genes Dev., 13, pp.2412~2424 (1999)
- Kong YY., "OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis", Nature., 397, pp.315~323 (1999)
- Jimi E., "Osteoclast differentiation factor acts as a multifunctional regulator in murine osteoclast differentiation and function", J Immunol., 163, pp.434~442 (1999)
- Lee SE., "The phosphatidylinositol 3-kinase, p38, and extracellular signal-regulated kinase pathways are involved in osteoclast differentiation", Bone., 30, pp.71~77 (2002)
- Iotsova V., "Osteopetrosis in mice lacking NF-kappaB1 and NF-kappaB2", Nat Med., 3, pp.1285~1289 (1997)
- Wei S., "Receptor activator of nuclear factor-kappa b ligand activates nuclear factor-kappa b in osteoclast precursors", Endocrinology., 142, pp.1290~1295 (2001)
- Datta SR., "Cellular survival: a play in three Akts", Genes Dev., 13, pp.2905~2927 (1999)
- Zhang C, "DC-STAMP, the key fusion-mediating molecule in osteoclastogenesis", J Cell Physiol, 229, pp.1330~1335 (2014)
- Roodman GD., "Paget disease of bone", J Clin Invest., 115, pp.200~208 (2005)
- Riba J., "Human pharmacology of ayahuasca: subjective and cardiovascular effects, monoamine metabolite excretion, and pharmacokinetics", J Pharmacol Exp Ther., 306, pp.73~83 (2003)
- Del Valle Mendoza J., "Antiviral activity of maca (Lepidium meyenii) against human influenza virus", Asian Pac J Trop Med., 7S1, pp.S415~420 (2014)
- Arora RB., "Anti-inflammatory studies on Curcuma longa(turmeric)", Indian J Med Res., 59, pp.1289~1295 (1971)
- Manhas A., "Curcuma oil reduces endothelial cell-mediated inflammation in postmyocardial ischemia", reperfusion in rats, 2014, pp.64, 228~236