Fibroblast growth factor 21 plays an inhibitory role in vascular calcification in vitro through OPG/RANKL system

Fangying Cao1, Xiaoxiao Liu1, Xiangrong Cao2

  • 1Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China.

Insights

Fibroblast growth factor (FGF)-21 effectively reduces vascular calcification by decreasing mineral deposition and apoptosis in vascular smooth muscle cells (VSMCs). FGF21 acts through the OPG/RANKL system and PI3K/AKT and p38 pathways.

Area of Science:

  • Biomedical Science
  • Cell Biology
  • Vascular Biology

Background:

  • Vascular calcification is a common condition linked to poor outcomes, with limited therapeutic options.
  • Fibroblast growth factor (FGF)-21 shows potential for treating vascular calcification due to its metabolic and anti-atherosclerotic benefits.

Purpose of the Study:

  • To investigate the therapeutic effects of FGF21 on vascular smooth muscle cell (VSMC) calcification.
  • To elucidate the molecular mechanisms underlying FGF21's action in preventing VSMC calcification.

Main Methods:

  • Rat VSMCs were cultured in a calcifying medium for 9 days.
  • FGF21 treatment was applied, and its effects on mineral deposition, apoptosis, and gene/protein expression were analyzed.
  • Key signaling pathways (PI3K/AKT, p38) and molecular markers (OPG, RANKL, ALP, RUNX-2) were assessed.

Main Results:

  • FGF21 significantly reduced mineral deposition and apoptosis in VSMCs.
  • FGF21 downregulated osteoblastic markers (BMP-2, ALP, RUNX-2, RANKL) and upregulated osteoprotegerin (OPG).
  • FGF21 promoted AKT phosphorylation while suppressing p38; OPG knockdown reversed these effects and impaired FGF21's anti-apoptotic and anti-calcific actions.

Conclusions:

  • FGF21 inhibits VSMC calcification by modulating the OPG/RANKL system.
  • The protective effects of FGF21 involve the regulation of p38 and PI3K/AKT signaling pathways.

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