Parathyroid Hormone Induces Expression of the Inducible cAMP Early Repressor in Osteoblastic MC3T3‐E1 Cells and Mouse Calvariae

• Published in: Journal of bone and mineral research 1998-12, Vol.13 (12), p.1846-1851
• Main Authors: Tetradis, Sotirios, Nervina, Jeanne M., Nemoto, Ken, Kream, Barbara E.
• Format: Article
• Language: English
• Subjects: 3T3 Cells; Animals; Biological and medical sciences; Cyclic AMP - biosynthesis; Cyclic AMP Response Element Modulator; Cyclic AMP-Dependent Protein Kinases - metabolism; Cycloheximide - pharmacology; Cyclooxygenase 2; DNA-Binding Proteins - biosynthesis; DNA-Binding Proteins - genetics; Female; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation - drug effects; Introns; Isoenzymes - metabolism; Mice; Osteoblasts - drug effects; Osteoblasts - metabolism; Parathyroid Hormone - pharmacology; Prostaglandin-Endoperoxide Synthases - metabolism; Protein Synthesis Inhibitors - pharmacology; Repressor Proteins - biosynthesis; Repressor Proteins - genetics; Skeleton and joints; Skull; Vertebrates: osteoarticular system, musculoskeletal system
• ISSN: 0884-0431; 1523-4681
• DOI: 10.1359/jbmr.1998.13.12.1846

Parathyroid hormone (PTH) regulates gene expression in skeletal osteoblasts mainly through the cAMP–protein kinase A (PKA) pathway. In neuroendocrine cells, activation of the cAMP–PKA signaling pathway leads to induction of the inducible cAMP early repressor (ICER), which is transcribed from an intronic promoter of the CREM gene and acts as a transcriptional repressor. To investigate whether PTH induces ICER expression in osteoblastic cells, RNA from MC3T3‐E1 cells was subjected to reverse transcriptase‐polymerase chain reaction using primers spanning the ICER sequence. Amplified products were subcloned, sequenced, and used as a probe for Northern blot analysis. In MC3T3‐E1 cells, PTH induced ICER mRNA levels, which peaked at 2 h and declined to baseline by 8 h. Cycloheximide caused superinduction of ICER mRNA in response to PTH. In cultured mouse calvariae, PTH also induced ICER mRNA accumulation, which peaked at 2 h and returned almost to baseline by 10 h. Overexpression of ICER IIγ decreased both baseline and PTH‐stimulated prostaglandin G/H synthase 2 promoter activity in MC3T3‐E1 cells. The induction of ICER represents a novel mechanism by which PTH regulates gene expression in osteoblastic cells.