FGF19 induces the cell cycle arrest at G2-phase in chondrocytes

Hao Chen1, Jiazhou Li1, Caixia Pi1

  • 1State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, 610041, Chengdu, China.

Cell Death Discovery
|July 15, 2023
PubMed

Insights

Fibroblast growth factor 19 (FGF19) halts chondrocyte proliferation by inducing G2 cell cycle arrest. This occurs via the FGFR4-p38/MAPK pathway, impacting key cell cycle regulators.

Area of Science:

  • Skeletal biology
  • Cell cycle regulation
  • Endocrinology

Background:

  • Fibroblast growth factor 19 (FGF19) is a potential therapeutic for skeletal disorders.
  • The precise role of FGF19 in skeletal cell cycle progression remains unclear.

Purpose of the Study:

  • To investigate the effect of FGF19 on chondrocyte proliferation and cell cycle progression.
  • To elucidate the molecular mechanisms underlying FGF19-induced cell cycle regulation in chondrocytes.

Main Methods:

  • Chondrocyte culture and treatment with FGF19.
  • Analysis of cell cycle phase distribution (e.g., flow cytometry).
  • Western blotting to assess protein expression (e.g., cdk1, cyclinb1, chk1, gadd45a, p38/MAPK).
  • Inhibitor experiments targeting FGFR4 and p38/MAPK signaling.

Main Results:

  • FGF19 significantly reduced chondrocyte proliferation and induced G2 phase cell cycle arrest.
  • FGF19 regulated the expression of cell cycle proteins including cdk1/cyclinb1, chk1, and gadd45a.
  • FGF19-mediated arrest was dependent on its interaction with β-Klotho (KLB) and the receptor FGFR4.
  • Activation of the p38/MAPK signaling pathway was crucial for FGF19-induced cell cycle arrest.

Conclusions:

  • FGF19 induces G2 phase cell cycle arrest in chondrocytes.
  • The FGFR4-p38/MAPK signaling axis mediates FGF19's effects on chondrocyte cell cycle progression.
  • This study provides novel insights into FGF19's role in skeletal cell biology and potential therapeutic applications.

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