Transcriptional induction of prostaglandin G/H synthase-2 by basic fibroblast growth factor.
In serum-free mouse osteoblastic MC3T3-E1 cells, basic fibroblastic growth factor (bFGF) induced mRNA and protein for prostaglandin G/H synthase-2 (PGHS-2), the major enzyme in arachidonic acid (AA) conversion to prostaglandins. mRNA accumulation peaked at 1 h with bFGF 1 nM. In cells stably transfected with a 371-bp PGHS-2 promoter-luciferase reporter, bFGF stimulated luciferase activity, which peaked at 2-3 h with bFGF 1-10 nM. In the presence of exogenous AA, bFGF stimulated PGE2 production, which paralleled luciferase activity. In serum-free neonatal mouse calvarial cultures, bFGF stimulated PGE2 production in the absence of exogenous AA. bFGF stimulated PGHS-2 mRNA accumulation, which peaked at 2-4 h and then decreased; there were later mRNA elevations at 48 and 96 h that were inhibited by indomethacin. In both MC3T3-E1 cells and neonatal calvariae, bFGF produced smaller and slower increases in PGHS-1 mRNA levels than for PGHS-2. bFGF stimulated bone resorption in mouse calvariae with a maximal increase of 80% at 1 nM. Stimulation was partially inhibited by nonsteroidal anti-inflammatory drugs. We conclude that bFGF rapidly stimulates PGE2 production in osteoblasts, largely through transcriptional regulation of PGHS-2, and that prostaglandins mediate some of bFGF's effects on bone resorption.
Kawaguchi
H
H
Department of Medicine, University of Connecticut Health Center, Farmington 06030, USA.
Pilbeam
C C
CC
Gronowicz
G
G
Abreu
C
C
Fletcher
B S
BS
Herschman
H R
HR
Raisz
L G
LG
Hurley
M M
MM
D000818:Animals; D000831:Animals, Newborn; D016590:Aphidicolin / Q000494:pharmacology; D001862:Bone Resorption / Q000201:enzymology; D016895:Culture Media, Serum-Free; D015232:Dinoprostone / Q000096:biosynthesis; D004790:Enzyme Induction / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D007527:Isoenzymes / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D010006:Osteoblasts / Q000187:drug effects* / Q000201:enzymology; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis* / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D012886:Skull; D014158:Transcription, Genetic / Q000187:drug effects*
D016895:Culture Media, Serum-Free; D007527:Isoenzymes; D011993:Recombinant Fusion Proteins; D016222:Fibroblast Growth Factor 2; D016590:Aphidicolin; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D007213:Indomethacin