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

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 mu M 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 mu M chelerythrine chloride or by prolonged stimulation with 50 ng/ml tetradecanoyl phorbol acetate (TPA) attenuated the induction of Egr-1 mRNA by 2 mu M PGE(2). These data indicate that in MC3T3-E1 cells, PGE(2) increases Egr-1 mRNA levels via a protein kinase C-dependent pathway.