Fibroblast growth factor 2 induction of the osteocalcin gene requires MAPK activity and phosphorylation of the

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Guozhi Xiao1, Di Jiang, Rajaram Gopalakrishnan

  • 1Department of Periodontics, School of Dentistry, University of Michigan, Ann Arbor, Michigan 48109-1078, USA.

The Journal of Biological Chemistry
|July 12, 2002
PubMed

Insights

Fibroblast growth factor 2 (FGF-2) activates osteocalcin gene expression in bone cells. This process involves the MAPK pathway, leading to Runx2 phosphorylation and enhanced bone formation.

Area of Science:

  • Bone Biology
  • Cell Signaling
  • Molecular Endocrinology

Background:

  • Fibroblast growth factor 2 (FGF-2) is crucial for bone formation and osteoblast activity.
  • The precise molecular mechanisms of FGF-2 action in bone cells remain largely undefined.
  • The mitogen-activated protein kinase (MAPK) pathway is a key signaling route for FGFs.

Purpose of the Study:

  • To elucidate the mechanism by which FGF-2 regulates the mouse osteocalcin gene in preosteoblastic cells.
  • To investigate the role of the MAPK pathway and the transcription factor Runx2 in FGF-2-mediated osteocalcin gene expression.

Main Methods:

  • MC3T3-E1 preosteoblastic cells and mouse bone marrow stromal cells were treated with FGF-2.
  • Osteocalcin mRNA and promoter activity were measured.
  • Phosphorylation of ERK1/2 and Runx2 was assessed.
  • The effect of the MAPK inhibitor U0126 and Runx2 deletion studies were performed.

Main Results:

  • FGF-2 dose- and time-dependently stimulated osteocalcin mRNA and promoter activity.
  • This stimulation was dependent on Runx2 and its DNA binding site.
  • FGF-2 increased phosphorylation of ERK1/2 and subsequently Runx2.
  • Inhibition of ERK1/2 blocked FGF-2 effects, confirming MAPK pathway involvement.
  • The C-terminal PST domain of Runx2 was essential for the FGF-2 response.

Conclusions:

  • FGF-2 activates osteocalcin gene expression via the MAPK pathway in preosteoblastic cells.
  • Runx2 is phosphorylated and activated by FGF-2 through MAPK signaling.
  • This study demonstrates FGF-2's significant role in regulating Runx2 function and bone formation.

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