Prostaglandin E 2 induces Egr-1 mRNA in MC3T3-E1 osteoblastic cells by a protein kinase C-dependent pathway

Abstract

Prostaglandin E 2 (PGE 2) plays an important role in the regulation of osteoblast metabolism. However, the nuclear signal transduction mechanisms involved in the actions of PGE 2 have not been clearly defined. One mechanism may involve induction of immediate early genes such as the transcription factor Egr-1. In the present study, we examined the effects of PGE 2 on induction of Egr-1 mRNA in MC3T3-E1 osteoblasts. Time course studies with 2 μM PGE 2 showed maximal induction of Egr-1 mRNA at 30 min. In cells pretreated with cycloheximide (CHX), induction of Egr-1 mRNA reached a maximum at 60 min and remained elevated for at least 240 min. Preincubation with CHX was associated with superinduction of Egr-1. Inhibition of protein kinase C activity by pretreatment with 1 μM chelerythrine chloride or by prolonged stimulation with 50 ng/ml tetradecanoyl phorbol acetate (TPA) attenuated the induction of Egr-1 mRNA by 2 μM PGE 2. These data indicate that in MC3T3-E1 cells, PGE 2 increases Egr-1 mRNA levels via a protein kinase C-dependent pathway.