Parathyroid hormone regulates the expression of fibroblast growth factor-2mRNA and fibroblast growth factor receptor mRNA in osteoblastic cells

We examined the effect of parathyroid hormone (PTH) on basic fibroblast gro wth factor-2 (FGF-2) and FGF receptor (FGFR) expression in osteoblastic MC3 T3-E1 cells and in neonatal mouse calvariae. Treatment of MC3T3-E1 cells wi th PTH(1-34) (10(-8)M) or forskolin (FSK; 10(-5)M) transiently increased a 7 kb FGF-2 transcript with a peak at 2 h. The PTH increase in FGF-2 mRNA wa s maintained in the presence of cycloheximide. PTH also increased FGFR-1 mR NA at 2 h and transiently increased FGFR-2 mRNA at 1 h. FGFR-3 and FGFR-4 m RNA transcripts were not detected in MC3T3-E1 cells. In cells transiently t ransfected with an 1800-bp FGF-2 promoter-luciferase reporter, PTH and FSK increased luciferase activity at 2 h and 4 h. Immunohistochemistry showed t hat PTH and FSK increased FGF-2 protein labeling in the nuclei of MC3T3-E1 cells. PTH also increased FGF-2 mRNA, and FGFR-1 and FGFR-2 mRNA levels wit hin 30 minutes in neonatal mouse calvarial organ cultures. We conclude that PTH and cAMP stimulate FGF-2 mRNA abundance in part through a transcriptio nal mechanism. PTH also regulated FGFR gene expression. We hypothesize that some effects of PTH on bone remodeling may be mediated by regulation of FG F-2 and FGFR expression in osteoblastic cells.