Comparison of β-Adrenergic and Glucocorticoid Signaling on Clock Gene and Osteoblast-Related Gene Expressions in Human Osteoblast
Comparison of β-Adrenergic and Glucocorticoid Signaling on Clock Gene and Osteoblast-Related Gene Expressions in Human Osteoblast
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DOI：
10.3109/07420528.2011.636496
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发表时间：
2012-01-01
影响因子：
2.8
通讯作者：
Togari, Akifumi
中科院分区：
文献类型：
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作者：
Komoto, Shintaro;Kondo, Hisataka;Togari, Akifumi
大多数生物体表现出由内源性生物钟产生的昼夜节律，主生物钟存在于视交叉上核（SCN）中。来自SCN的输出信号被认为通过交感神经系统和体液途径将标准昼夜节律时间传递到外周组织。因此，作者在培养的人成骨细胞SaM-1细胞中检测了用β-肾上腺素能受体激动剂异丙肾上腺素或合成糖皮质激素地塞米松处理后时钟基因的表达。用10（-6）M异丙肾上腺素或10（-7）M地塞米松处理细胞2小时，并使用实时聚合酶链反应（PCR）分析测定基因表达。用异丙肾上腺素或地塞米松处理诱导生物钟基因人类周期1（hPer 1）、hPer 2、hPer 3和人脑和肌肉Arnt样蛋白1（hBMAL 1）的昼夜节律表达。异丙肾上腺素或地塞米松治疗后即刻使hPer 1和hPer 2升高，并引起hPer 1和hPer 2的昼夜节律振荡，在48 h内出现3个高峰。异丙肾上腺素或地塞米松处理后hPer 3表达出现一个高峰。异丙肾上腺素或地塞米松处理后hBMAL表达出现两个高峰，时间模式与其他时钟基因的表达相反。与异丙肾上腺素处理相比，地塞米松处理使所有时钟基因的振荡延迟2-6小时。作者还检测了成骨细胞相关基因h α-1 I型胶原（hCol 1a 1）、碱性磷酸酶（hALP）和骨钙素（hOC）的表达。异丙肾上腺素诱导hCol 1a 1的振荡，但不诱导hALP和hOC的振荡。另一方面，地塞米松诱导hCol 1a 1和hALP的振荡，而不是hOC。异丙肾上腺素在第一时相上调hCol 1a 1的表达，而地塞米松在第一时相下调hCol 1a 1和hALP的表达。（作者通讯：togariaf@dpc.agu.ac.jp）
Most living organisms exhibit circadian rhythms that are generated by endogenous circadian clocks, the master one being present in the suprachiasmatic nuclei (SCN). Output signals from the SCN are believed to transmit standard circadian time to peripheral tissue through sympathetic nervous system and humoral routes. Therefore, the authors examined the expression of clock genes following treatment with the beta-adrenergic receptor agonist, isoprenaline, or the synthetic glucocorticoid, dexamethasone, in cultured human osteoblast SaM-1 cells. Cells were treated with 10(-6) M isoprenaline or 10(-7) M dexamethasone for 2 h and gene expressions were determined using real-time polymerase chain reaction (PCR) analysis. Treatment with isoprenaline or dexamethasone induced the circadian expression of clock genes human period 1 (hPer1), hPer2, hPer3, and human brain and muscle Arnt-like protein 1 (hBMAL1). Isoprenaline or dexamethasone treatment immediately increased hPer1 and hPer2 and caused circadian oscillation of hPer1 and hPer2 with three peaks within 48 h. hPer3 expression had one peak after isoprenaline or dexamethasone treatment. hBMAL expression had two peaks after isoprenaline or dexamethasone treatment, the temporal pattern being in antiphase to that of the other clock genes. Dexamethasone treatment delayed the oscillation of all clock genes for 2-6 h compared with isoprenaline treatment. The authors also examined the expression of osteoblast-related genes h alpha-1 type I collagen (hCol1a1), halkaline phosphatase (hALP), and hosteocalcin (hOC). Isoprenaline induced oscillation of hCol1a1, but not hALP and hOC. On the other hand, dexamethasone induced oscillation of hCol1a1 and hALP, but not hOC. Isoprenaline up-regulated hCol1a1 expression, but dexamethasone down-regulated hCol1a1 and hALP expression in the first phase. (Author correspondence: togariaf@dpc.agu.ac.jp)