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Fluoride-induced c-Fos expression in MC3T3-E1 osteoblastic cells
被引:13
作者:
Iwatsuki, Mamiko
[1
]
Matsuoka, Masato
[1
]
机构:
[1] Tokyo Womens Med Univ, Dept Hyg & Publ Hlth 1, Tokyo 1628666, Japan
基金:
日本学术振兴会;
关键词:
c-Fos;
fluoride;
MC3T3-E1 osteoblast cell line;
mitogen-activated protein kinases;
osteoprotegerin;
ENDOPLASMIC-RETICULUM STRESS;
AFFECTS CALCIUM HOMEOSTASIS;
ACTIVATED PROTEIN-KINASE;
KAPPA-B LIGAND;
PROTEASOMAL DEGRADATION;
PARATHYROID-HORMONE;
RECEPTOR ACTIVATOR;
GENE;
PHOSPHORYLATION;
BONE;
D O I:
10.3109/15376516.2015.1129570
中图分类号:
R99 [毒物学(毒理学)];
学科分类号:
100405 ;
摘要:
Excessive systemic exposure to fluoride leads to disturbances of bone homeostasis. c-Fos is known to be essential in bone development by affecting osteoblast and osteoclast differentiation. In this study, we examined the effects of fluoride exposure on c-Fos expression and its regulatory signaling pathways in MC3T3-E1 mouse osteoblast cell line. c-fos mRNA level, c-Fos protein level and c-Fos DNA-binding activity were markedly increased, with a peak at 2 or 4h, in MC3T3-E1 cells exposed to sodium fluoride (NaF). Fra-1 protein, another member of Fos family, was also elevated, whereas FosB and Fra-2 proteins remained unchanged. NaF further induced phosphorylation of mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated protein kinase 1/2 (ERK1/2), ERK5, c-Jun NH2-terminal kinase and p38. NaF-induced expression of c-Fos protein was markedly suppressed with U0126, the inhibitor of both activated and non-activated forms of MAPK/ERK kinase 1/2 (MEK1/2) and BIX02189, the MEK5 inhibitor, but partially with SP600125, the JNK inhibitor and SB203580, the p38 inhibitor. Therefore, ERK1/2 and ERK5 signal transduction pathways are important for accumulating c-Fos. siRNA targeting against the mouse c-fos gene further enhanced NaF-induced up-regulation of osteoprotegerin (OPG), an inhibitor of osteoclastogenesis, suggesting that c-Fos might negatively regulate OPG expression induced by fluoride in osteoblastic cells.
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页码:132 / 138
页数:7
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