PARATHYROID-HORMONE INDUCES EXPRESSION OF THE INDUCIBLE CAMP EARLY REPRESSOR IN OSTEOBLASTIC MC3T3-E1 CELLS AND MOUSE CALVARIAE

Parathyroid hormone (PTH) regulates gene expression in skeletal osteob lasts mainly through the cAMP-protein kinase A (PKA) pathway. In neuro endocrine cells, activation of the cAMP-PKA signaling pathway leads to induction of the inducible cAMP early repressor (ICER), which is tran scribed from an intronic promoter of the CREM gene and acts as a trans criptional repressor, To investigate whether PTH induces ICER expressi on in osteoblastic cells, RNA from MC3T3-E1 cells was subjected to rev erse transcriptase-polymerase chain reaction using primers spanning th e ICER sequence, Amplified products were subcloned, sequenced, and use d as a probe for Northern blot analysis, In MC3T3-E1 cells, PTH induce d 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, Overexp ression of ICER II gamma decreased both baseline and PTH-stimulated pr ostaglandin G/H synthase 2 promoter activity in MC3T3-E1 cells. The in duction of ICER represents a novel mechanism by which PTH regulates ge ne expression in osteoblastic cells.