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

M M Hurley1, S Tetradis, Y F Huang

  • 1The University of Connecticut Health Center, Division of Endocrinology and Metabolism, Farmington, Connecticut 06030-1850, USA.

Insights

Parathyroid hormone (PTH) and cAMP stimulate fibroblast growth factor-2 (FGF-2) mRNA, partly via transcriptional mechanisms. PTH also regulates FGF receptor (FGFR) gene expression, suggesting a role in bone remodeling.

Area of Science:

  • Molecular Biology
  • Endocrinology
  • Cell Biology

Background:

  • Parathyroid hormone (PTH) is crucial for bone metabolism.
  • Fibroblast growth factor-2 (FGF-2) and its receptors (FGFRs) play roles in cell growth and differentiation.
  • The interplay between PTH and FGF-2/FGFR signaling in osteoblasts requires further elucidation.

Purpose of the Study:

  • To investigate the effect of PTH on FGF-2 and FGFR expression in osteoblastic cells and bone tissue.
  • To determine the molecular mechanisms underlying PTH-induced changes in FGF-2 and FGFR expression.

Main Methods:

  • Treatment of MC3T3-E1 osteoblastic cells and neonatal mouse calvariae with PTH(1-34) or forskolin (FSK).
  • Analysis of FGF-2 and FGFR mRNA and protein expression using RT-PCR, Western blotting, and immunohistochemistry.
  • Reporter gene assays to assess transcriptional activity of the FGF-2 promoter.

Main Results:

  • PTH and FSK increased FGF-2 mRNA and protein levels in MC3T3-E1 cells, with increased transcriptional activity.
  • PTH also upregulated FGFR-1 and FGFR-2 mRNA in both cell cultures and calvariae.
  • These effects were observed rapidly and, for FGF-2 mRNA, were maintained in the presence of cycloheximide.

Conclusions:

  • PTH and cAMP signaling pathways stimulate FGF-2 mRNA abundance, at least in part, through transcriptional regulation.
  • PTH modulates the expression of FGFR genes.
  • These findings suggest that PTH may influence bone remodeling by regulating FGF-2 and FGFR expression in osteoblasts.

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