Parathyroid hormone induces expression of the inducible cAMP early repressor in osteoblastic MC3T3-E1 cells and mouse calvariae

Sotirios Tetradis, Jeanne M. Nervina, Ken Nemoto, Barbara E. Kream

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1846-1851
Number of pages6
JournalJournal of Bone and Mineral Research
Volume13
Issue number12
DOIs
StatePublished - Dec 1998

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine

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