Transcriptional regulation of the cyclooxygenase-2 gene by diverse ligands in 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 [TNFalpha + IL1beta] rapidly induce expression of COX-2 protein in murine MC3T3-E1 osteogenic cells. Transient transfection studies using reporter constructs containing either wild-type COX-2 regulatory sequences or mutated cis-acting sequences linked to a luciferase reporter gene identify 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 osteoblasts. Induction of wild-type COX-2 reporter gene expression in MC3T3-E1 cells by all these agents involves signaling through the MEKK/JNK pathway and activation of both c-Jun and the C/EBP family of transcription factors.
Wadleigh
D J
DJ
Molecular Biology Institute, University of California-Los Angeles, Los Angeles, California, 90095, USA.
Herschman
H R
HR
D000818:Animals; D002478:Cells, Cultured; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D017930:Genes, Reporter; D007375:Interleukin-1 / Q000494:pharmacology; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics*; D008024:Ligands; D051379:Mice; D010006:Osteoblasts / Q000201:enzymology*; D010120:Oxytocics / Q000494:pharmacology; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis / Q000235:genetics*; D015533:Transcriptional Activation / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D007375:Interleukin-1; D007527:Isoenzymes; D008024:Ligands; D010120:Oxytocics; D010982:Platelet-Derived Growth Factor; D014409:Tumor Necrosis Factor-alpha; D016222:Fibroblast Growth Factor 2; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone