Prostaglandin E2 induces Egr-1 mRNA in MC3T3-E1 osteoblastic cells by a protein kinase C-dependent pathway

Prostaglandin E2 (PGE2) plays an important role in the regulation of osteoblast metabolism. However, the nuclear signal transduction mechanisms involved in the actions of PGE2 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 PGE2 on induction of Egr-1 mRNA in MC3T3-E1 osteoblasts. Time course studies with 2 microM PGE2 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 microM chelerythrine chloride or by prolonged stimulation with 50 ng/ml tetradecanoyl phorbol acetate (TPA) attenuated the induction of Egr-1 mRNA by 2 microM PGE2. These data indicate that in MC3T3-E1 cells, PGE2 increase Egr-1 mRNA levels via a protein kinase C-dependent pathway.