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

Biochem Biophys Res Commun. 1999 Nov 2;264(3):865-70. doi: 10.1006/bbrc.1999.1606.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cells, Cultured
  • Cyclooxygenase 2
  • Dinoprostone / pharmacology
  • Fibroblast Growth Factor 2 / pharmacology
  • Gene Expression Regulation, Enzymologic / drug effects
  • Genes, Reporter
  • Interleukin-1 / pharmacology
  • Isoenzymes / biosynthesis
  • Isoenzymes / genetics*
  • Ligands
  • Mice
  • Osteoblasts / enzymology*
  • Oxytocics / pharmacology
  • Platelet-Derived Growth Factor / pharmacology
  • Prostaglandin-Endoperoxide Synthases / biosynthesis
  • Prostaglandin-Endoperoxide Synthases / genetics*
  • Transcriptional Activation* / drug effects
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • Interleukin-1
  • Isoenzymes
  • Ligands
  • Oxytocics
  • Platelet-Derived Growth Factor
  • Tumor Necrosis Factor-alpha
  • Fibroblast Growth Factor 2
  • Cyclooxygenase 2
  • Prostaglandin-Endoperoxide Synthases
  • Dinoprostone