Differential Regulation of RGS-2 by Constant and Oscillating PTH Concentrations
| Autor: | C. P. Schmitt, Franz Schaefer, Otto Mehls, M. Hömme |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
medicine.medical_specialty
Anabolism Endocrinology Diabetes and Metabolism Parathyroid hormone Peptide hormone Biology Bone and Bones Endocrinology Dual Specificity Phosphatase 6 Cell Line Tumor Internal medicine Matrix Metalloproteinase 13 medicine Animals Orthopedics and Sports Medicine Receptor Receptor Parathyroid Hormone Type 1 Osteoblasts Dose-Response Relationship Drug Catabolism Parathyroid hormone receptor Dual Specificity Phosphatase 1 Radioimmunoassay Cyclic AMP-Dependent Protein Kinases Rats Dose–response relationship Gene Expression Regulation Parathyroid Hormone Insulin-Like Growth Factor Binding Protein 5 RGS Proteins hormones hormone substitutes and hormone antagonists Signal Transduction |
| Zdroj: | Calcified Tissue International. 84:305-312 |
| ISSN: | 1432-0827 0171-967X |
| DOI: | 10.1007/s00223-009-9222-1 |
| Popis: | PTH has diverse effects on bone metabolism: anabolic when given intermittently, catabolic when given continuously. The cellular mechanisms underlying the varying target cell response are not clear yet. PTH induces RGS-2, a member of the Regulator of G-protein Signaling protein family, via cAMP/PKA, and inactivates PKC-mediated signaling. To investigate intracellular signaling pathways with different PTH concentration-time patterns, we treated UMR 106-01 osteoblast-like cells in a perfusion system. PTH was administered intermittently (4 min/h, 10(-7) M) or continuously at an equivalent cumulative dose (6.6 x 10(-9) M). cAMP was measured using radioimmunoassay, mRNA levels using real-time rtPCR and ribonuclease protection assay, and protein levels using Western immunoblotting. A single PTH pulse transiently increased cAMP levels by 2000% +/- 1200%. In contrast to continuous PTH exposure, cAMP induction remained unchanged with intermittent PTH, ruling out desensitization of the PTH receptor. In continuously perfused cells, RGS-2 abundance was three to five times higher than in cells intermittently exposed to PTH for up to 12 h. MKP-1 and -3 were significantly less induced with pulsatile PTH; exposure-mode-dependent differences in MMP-13 and IGFBP-5 were small. Pulsatile but not continuous PTH administration prevents PTHrP receptor desensitization and accumulation of RGS-2 in osteoblasts, which should preserve PKC-dependent signaling. |
| Databáze: | OpenAIRE |
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