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 Ih 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 PGE(2) production, which paralleled luciferase activity, In serum-free neonatal mouse calvarial cultures, bFGF stimulated PGE, 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 PGE(2) production in osteoblasts, largely through transcriptional regulation of PGHS-2, and that prostaglandins mediate some of bFGF's effects on bone resorption.