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Parathyroid Hormone Induces Expression of the Inducible cAMP Early Repressor in Osteoblastic MC3T3‐E1 Cells and Mouse Calvariae
Author(s) -
Tetradis Sotirios,
Nervina Jeanne M.,
Nemoto Ken,
Kream Barbara E.
Publication year - 1998
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1359/jbmr.1998.13.12.1846
Subject(s) - parathyroid hormone , repressor , cycloheximide , microbiology and biotechnology , messenger rna , gene expression , biology , northern blot , medicine , endocrinology , gene , protein biosynthesis , calcium , biochemistry
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.