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Upregulation of PTH receptor mRNA expression by dexamethasone in UMR‐106 osteoblast‐like cells
Author(s) -
Haramoto N,
Kawane T,
Horiuchi N
Publication year - 2007
Publication title -
oral diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.953
H-Index - 87
eISSN - 1601-0825
pISSN - 1354-523X
DOI - 10.1111/j.1601-0825.2006.01234.x
Subject(s) - parathyroid hormone , downregulation and upregulation , osteoblast , glucocorticoid receptor , messenger rna , endocrinology , medicine , receptor , glucocorticoid , dexamethasone , biology , gene expression , chemistry , gene , in vitro , biochemistry , calcium
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.