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Fisetin and resveratrol exhibit senotherapeutic effects and suppress cellular senescence in osteoarthritic cartilage-derived chondrogenic progenitor cells

  • 0Department of Anatomy, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, 160012, India.
European Journal of Pharmacology +

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April 6, 2025

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April 6, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

Fisetin and resveratrol, natural compounds, were found to suppress cellular senescence in knee osteoarthritis (OA) chondrogenic progenitor cells (CPCs). These senotherapeutics reduced senescence markers and inflammatory SASP factors, offering potential OA treatment strategies.

Area Of Science

  • Biomedical Science
  • Cell Biology
  • Osteoarthritis Research

Background

  • Articular cartilage in knee osteoarthritis (OA) patients features chondrogenic progenitor cells (CPCs) exhibiting cellular senescence and a senescence-associated secretory phenotype (SASP).
  • Cellular senescence contributes to OA pathogenesis, making it a target for therapeutic intervention.

Purpose Of The Study

  • To investigate the senotherapeutic potential of fisetin and resveratrol in suppressing cellular senescence in CPCs from OA patients.
  • To evaluate the effects of fisetin and resveratrol on senescence markers and SASP factors in OA-derived CPCs.

Main Methods

  • In vitro treatment of CPCs with varying concentrations of fisetin and resveratrol.
  • Assessment of cell viability, senescence index, and expression of senescence markers (p53, p38MAPK).
  • Analysis of SASP-related genes/proteins (MMP-9, MMP13) and inflammatory mediators (IL-1β, TGF-β, IL-6).
  • In silico molecular docking to confirm binding affinity to OA-related proteins.

Main Results

  • Fisetin and resveratrol were non-cytotoxic to CPCs at tested concentrations (5μM-100μM).
  • Both compounds significantly decreased the senescence index and downregulated p53 and p38MAPK expression.
  • Expression of SASP factors (MMP-9, MMP13) and inflammatory mediators (IL-1β, TGF-β, IL-6) was reduced.
  • In silico analysis supported the binding affinity of fisetin and resveratrol to OA-related targets.

Conclusions

  • Fisetin and resveratrol effectively dampen cellular senescence and reduce the SASP in OA-derived CPCs, primarily through p53 pathway modulation.
  • These natural compounds demonstrate potential as senotherapeutics for knee osteoarthritis, targeting cellular senescence and associated inflammation.

Keywords:

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