Upregulation of PTH receptor mRNA expression by dexamethasone in UMR-106 osteoblast-like cells
Upregulation of PTH receptor mRNA expression by dexamethasone in UMR-106 osteoblast-like cells
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DOI：
10.1111/j.1601-0825.2006.01234.x
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发表时间：
2007-01-01
期刊：
影响因子：
3.8
通讯作者：
Horiuchi, N.
中科院分区：
文献类型：
--
作者：
Haramoto, N.;Kawane, T.;Horiuchi, N.
目的：糖皮质激素影响甲状旁腺激素(PTH)的受体相互作用，甲状旁腺激素对成骨细胞功能至关重要。由于受体mRNA与糖皮质激素之间的联系机制尚不完全清楚，我们研究了人工合成的糖皮质激素地塞米松(Dex)对大鼠成骨样UMR-106细胞甲状旁腺素受体(PTH1R)mRNA表达的调节。材料和方法：将UMR-106细胞暴露于10(-8)~10(-5)M Dex，同时部分细胞还暴露于转录抑制物(DRB)24 h。用酶联免疫吸附试验检测PTH刺激的细胞周期AMP活性。Northern分析检测PTH1R基因的表达。结果：地塞米松可剂量依赖性地增加PTH刺激的腺苷环化酶的活性，地塞米松显著增加PTH1R的转录活性，但对转录活性无明显影响。结论：在成骨细胞样细胞中，地塞米松诱导PTH1R mRNA表达上调，进而增加功能性PTH受体的表达。这是由于转录后机制增加了mRNA的稳定性。
OBJECTIVES: Glucocorticoids influence receptor interactions of the parathyroid hormone (PTH) that are crucial for osteoblast function. As mechanisms linking receptor mRNA with glucocorticoids are incompletely understood, we investigated regulation of PTH receptor (PTH1R) mRNA expression in rat osteoblast-like UMR-106 cells by using dexamethasone (Dex), a synthetic glucocorticoid.MATERIALS AND METHODS: UMR-106 cells were exposed to 10(-8) to 10(-5) M Dex, while some cells were also exposed to a transcriptional inhibitor (DRB) for 24 h with or without Dex. PTH-stimulated cyclicAMP activities were measured by an enzyme-linked immunosorbent assay. PTH1R mRNA was determined by Northern analysis. Transcriptional activities were measured as heretogeneous nuclear PTH1R RNA and also as luciferase activity in constructs, including the PTH1R gene promoter.RESULTS: Dexamethasone dose-dependently increased PTH-stimulated adenylyl cyclase activity at 72 h. Dex markedly increased PTH1R mRNA accumulation, but did not change transcriptional activity. PTH1R mRNA stability was significantly increased by Dex in transcriptionally arrested cells.CONCLUSION: In osteoblast-like cells, Dex induced upregulation of PTH1R mRNA followed by increased functional PTH receptor expression. This was caused by posttranscriptional mechanisms increasing mRNA stability.