Thyroid hormone non-genomically suppresses Src thereby stimulating osteocalcin expression in primary mouse calvarial osteoblasts

Thyroid hormone non-genomically suppresses Src thereby stimulating osteocalcin expression in primary mouse calvarial osteoblasts
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DOI:
10.1016/j.bbrc.2009.06.131
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发表时间:
2009-09-11
影响因子:
3.1
通讯作者:
Kambe, Fukushi
Kambe, Fukushi
中科院分区:
生物学4区
文献类型:
--
作者:
Asai, Shuji;Cao, Xia;Kambe, Fukushi

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为了进一步了解甲状腺激素(T3)的非基因组作用,我们研究了Src是否受T3的控制,从新生小鼠制备的原代颅骨成骨细胞。用T3处理细胞迅速降低Src Y416自磷酸化,随后降低磷酸化的细胞外信号调节激酶,表明T3非基因组抑制Src活性。此外,这种T3效应是快速和持久的,并与骨钙素(OC)的表达增加有关。为了证实Src对T3对OC表达的影响的贡献,在成骨细胞中过表达组成型活性Src(Y527F)。在这样的细胞中,Y416磷酸化显着增加,即使在T3的存在下,和T3依赖的OC表达显着减弱。本研究证实了T3在原代小鼠成骨细胞中的一种新的非基因组作用,通过该作用T3抑制Src从而刺激OC表达。(C)2009 Elsevier Inc. All rights reserved.
To provide further insights into non-genomic action of thyroid hormone (T3), we investigated whether Src is under control of T3 in primary calvarial osteoblasts prepared from neonatal mice. Treatment of the cells with T3 rapidly decreased Src Y416 autophosphorylation, followed by the decrease of phosphorylated extracellular signal-regulated kinases, suggesting that T3 non-genomically suppresses Src activity. Furthermore, this T3 effect was rapid and Persistent, and was associated with the increased expression of osteocalcin (OC). To confirm the contribution of Src to the effect of T3 on OC expression, a constitutively active Src (Y527F) was overexpressed in osteoblasts. In such cells, Y416 phosphorylation was markedly increased even in the presence of T3, and T3-dependent expression of OC was markedly attenuated. The present study demonstrates a novel, non-genomic action of T3 in primary Mouse osteoblasts, by which T3 suppresses Src thereby stimulating OC expression. (C) 2009 Elsevier Inc. All rights reserved.