Transcriptional regulation of the cyclooxygenase-2 gene by diverse ligandsin murine osteoblasts

Osteoblasts produce prostaglandins in response to a wide variety of stimuli . Induced prostaglandin synthesis is generally the consequence of elevated cyclooxygenase-2 (COX-2) expression. Agents as diverse as serum, bFGF, PDGF , PGE(2), or [TNF alpha + IL1 beta] rapidly induce expression of COX-2 prot ein in murine MC3T3-E1 osteogenic cells. Transient transfection studies usi ng reporter constructs containing either mild-type COX-2 regulatory sequenc es or mutated cis-acting sequences linked to a luciferase reporter gene ide ntify a CRE site and two NF-IL6 (C/EBP) sites which play important roles in the regulation of COX-2 expression in response to all these agents in oste oblasts. Induction of wild-type COX-2 reporter gene expression in MC3T3-E1 cells by all these agents involves signaling through the MEKK/JNK pathway a nd activation of both c-Jun and the C/EBP family of transcription factors. (C) 1999 Academic Press.