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Fibroblast growth factor receptor 1 regulates the differentiation and activation of osteoclasts through Erk1/2

Xiumin Lu1, Nan Su, Jing Yang

  • 1State Key Laboratory of Trauma, Burns and Combined Injury, Trauma Center, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing 400042, China.

Biochemical and Biophysical Research Communications
|October 6, 2009
PubMed

Insights

Fibroblast growth factor receptor 1 (FGFR1) is essential for osteoclast differentiation and function. FGFR1 deficiency in mice impairs bone remodeling by reducing osteoclast number and activity.

Area of Science:

  • Bone Biology
  • Cell Signaling
  • Skeletal Physiology

Background:

  • Osteoclasts are critical for bone remodeling, and their dysfunction contributes to bone diseases.
  • Fibroblast growth factor receptor 1 (FGFR1) signaling pathways are implicated in various cellular processes, but its specific role in osteoclast biology requires further elucidation.

Purpose of the Study:

  • To investigate the direct role and underlying mechanisms of FGFR1 signaling in osteoclast differentiation and activation.
  • To determine the impact of FGFR1 deficiency on bone remodeling in vivo and osteoclast function in vitro.

Main Methods:

  • Conditional inactivation of FGFR1 in mouse bone marrow monocytes and mature osteoclasts.
  • In vitro differentiation assays to assess osteoclast formation and tartrate-resistant acid phosphatase (TRAP) positive osteoclast counts.
  • Bone resorption assays to evaluate the functional capacity of osteoclasts.
  • Gene expression analysis (TRAP, MMP-9) and Western blotting for Erk1/2 mitogen-activated protein (MAP) kinase phosphorylation.

Main Results:

  • Mice with FGFR1 deficiency (Fgfr1(-/-)) displayed dysregulated bone remodeling, characterized by a reduced number of osteoclasts and impaired osteoclast function.
  • In vitro studies showed significantly diminished TRAP-positive osteoclast formation from Fgfr1(-/-) bone marrow monocytes.
  • Bone resorption activity of mature osteoclasts from Fgfr1(-/-) mice was suppressed, with downregulated expression of key osteoclastic genes (TRAP, MMP-9) and decreased Erk1/2 MAP kinase phosphorylation.

Conclusions:

  • FGFR1 signaling is indispensable for the complete differentiation and activation of osteoclasts.
  • FGFR1 plays a crucial role in regulating osteoclast number, function, and the expression of genes vital for bone resorption.
  • Targeting FGFR1 signaling may offer therapeutic potential for bone diseases associated with osteoclast dysfunction.

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