Formoterol and isoproterenol induce c-fos gene expression in osteoblast-like cells by activating β2-adrenergic receptors
Formoterol and isoproterenol induce c-fos gene expression in osteoblast-like cells by activating β2-adrenergic receptors
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DOI：
10.1016/s8756-3282(98)00026-x
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发表时间：
1998-05-01
期刊：
影响因子：
4.1
通讯作者：
Bilbe, G
中科院分区：
文献类型：
--
作者：
Kellenberger, S;Muller, K;Bilbe, G
福莫特罗是一种β（2）-肾上腺素能激动剂，在卵巢切除大鼠模型中显示对骨具有合成代谢作用。然而，这些研究没有确定福莫特罗的作用是通过直接作用于骨细胞本身还是间接通过对肌肉的合成代谢作用。为了解决福莫特罗是否会直接影响成骨细胞功能的问题，我们研究了人成骨细胞样细胞中β-肾上腺素能受体（β AR）的表达模式以及与基因表达的功能偶联。北方印迹分析显示，β AR亚型在成骨样细胞系TE-85、SaOS-2、MG-63和OHS-4中有不同水平的表达，β（1）AR在SaOS-2、OHS-4和TE-85中有表达，而MG-63细胞中无表达。β 2 AR在MG-63细胞中的表达水平高于TE-85和SaOS-2细胞，但在OHS-4细胞中未检测到。PCR分析结果与北方印迹分析结果一致，只是在三个人原代成骨细胞cDNA中的一个中发现了β（3）AR表达。在任何成骨样细胞系中均未发现β（3）AR表达。非特异性PAR激动剂异丙肾上腺素和β（2）AR特异性激动剂福莫特罗以立即早期的方式诱导培养的SaOS-2细胞中c-fos基因表达。β 2 AR特异性拮抗剂ICI 118551可抑制c-fos基因的表达，而β 1 AR特异性拮抗剂CGP 20712则不能抑制c-fos基因的表达，表明c-fos基因的表达是由β 2 AR特异性介导的，异丙肾上腺素和福莫特罗均通过增加cAMP而诱导c-fos基因的表达，而cAMP/PKA通路则被激活; PKA抑制剂H89抑制c-fos基因表达。因此，β AR在成骨细胞样细胞中表达，并通过β（2）AR、CAMP水平的增加和PKA依赖性途径的激活与c-fos基因表达偶联。(C)1998年，Elsevier Science Inc. All rights reserved.
Formoterol, a beta(2)-adrenergic agonist has been shown in ovariectomized rat models to have anabolic effects on bone. However, those studies did not determine whether the effect of formoterol was by a direct action on bone cells themselves or indirectly via anabolic action on muscle. To address the question of whether formoterol could directly affect osteoblast function we investigated the expression patterns of beta-adrenergic receptors (beta ARs) in human osteoblast-like cells and functional coupling to gene expression. Northern blot analysis showed that beta AR subtypes are expressed at different levels in the osteoblast-like cell lines TE-85, SaOS-2, MG-63, and OHS-4, beta(1)AR expression was found in SaOS-2, OHS-4, and TE-85, but not MG-63 cells. beta(2)ARs are expressed at higher levels in MG-63 cells than in TE-85 and SaOS-2 cells, but were not detected in OHS-4 cells. PCR analysis paralleled the northern blot analysis except that beta(3)AR expression was found in one of three human primary osteoblast cDNAs tested. beta(3)AR expression was not found in any of the osteoblast-like cell lines. The nonspecific PAR agonist, isoproterenol, and the beta(2)AR-specific agonist, formoterol, induced c-fos gene expression in cultured SaOS-2 cells in an immediate early fashion. This effect was inhibited by the beta(2)AR-specific antagonist, ICI 118551, but not by the beta(1)AR-specific antagonist, CGP 20712, indicating that induction of c-fos gene expression is specifically mediated by beta(2)ARs, c-fos gene expression was induced by both isoproterenol and formoterol via increases in cAMP, which in turn activated the cAMP/PKA pathway; the PKA inhibitor, H89, inhibited c-fos gene expression, Thus, beta ARs are expressed, in osteoblast-like cells and are coupled to c-fos gene expression via the beta(2)AR, increases in CAMP levels and activation of a PKA-dependent pathway. (C) 1998 by Elsevier Science Inc. All rights reserved.