Endogenous FGF-2 is critically important in PTH anabolic effects on bone

Maria Giovanna Sabbieti, Dimitrios Agas, Liping Xiao, Luigi Marchetti, J. Douglas Coffin, Thomas Doetschman, Marja M. Hurley

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50 Scopus citations

Abstract

Parathyroid hormone (PTH) increases fibroblast growth factor receptor-1 (FGFR1) and fibroblast growth factor-2 (FGF-2) expression in osteoblasts and the anabolic response to PTH is reduced in Fgf2-/- mice. This study examined whether candidate factors implicated in the anabolic response to PTH were modulated in Fgf2-/- osteoblasts. PTH increased Runx-2 protein expression in Fgf2+/+ but not Fgf2-/- osteoblasts. By immunocytochemistry, PTH treatment induced nuclear accumulation of Runx-2 only in Fgf2+/+ osteoblasts. PTH and FGF-2 regulate Runx-2 via activation of the cAMP response element binding proteins (CREBs). Western blot time course studies showed that PTH increased phospho-CREB within 15 min that was sustained for 24 h in Fgf2+/+but had no effect in Fgf2-/- osteoblasts. Silencing of FGF-2 in Fgf2+/+ osteoblasts blocked the stimulatory effect of PTH on Runx-2 and CREBs phosphorylation. Studies of the effects of PTH on proteins involved in osteoblast precursor proliferation and apoptosis showed that PTH increased cyclinD1-cdk4/6 protein in Fgf2+/+ but not Fgf2-/- osteoblasts. Interestingly, PTH increased the cell cycle inhibitor p21/waf1 in Fgf2-/- osteoblasts. PTH increased Bcl-2/Bax protein ratio in Fgf2+/+ but not Fgf2-/- osteoblasts. In addition PTH increased cell viability in Fgf2+/+ but not Fgf2-/- osteoblasts. These data suggest that endogenous FGF-2 is important in PTH effects on osteoblast proliferation, differentiation, and apoptosis. Reduced expression of these factors may contribute to the reduced anabolic response to PTH in the Fgf2-/- mice. Our results strongly indicate that the anabolic PTH effect is dependent in part on FGF-2 expression. J. Cell. Physiol.219: 143-151,2009.

Original languageEnglish (US)
Pages (from-to)143-151
Number of pages9
JournalJournal of Cellular Physiology
Volume219
Issue number1
DOIs
StatePublished - Apr 1 2009

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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    Sabbieti, M. G., Agas, D., Xiao, L., Marchetti, L., Coffin, J. D., Doetschman, T., & Hurley, M. M. (2009). Endogenous FGF-2 is critically important in PTH anabolic effects on bone. Journal of Cellular Physiology, 219(1), 143-151. https://doi.org/10.1002/jcp.21661