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The influence of PPARγ mediated MAPK and NF-κB activation in AGEs stimulated apoptosis and autophagy in human chondrocytes

  • 0Department of Trauma Repair reconstructive surgery, Fenyang Hospital of Shanxi Province, Fen yang Hospital Affiliated to Shanxi Medical University, Fenyang, 032200, Shanxi, People's Republic of China.
Journal of Orthopaedics +

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June 13, 2025

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June 13, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

Advanced Glycation End Products (AGEs) increase osteoarthritis risk by promoting chondrocyte apoptosis and reducing autophagy. PPARγ activation with pioglitazone mitigates these effects by regulating MAPK and NF-κB pathways, suggesting a therapeutic potential for OA.

Area Of Science

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Background

  • Advanced Glycation End Products (AGEs) are implicated in osteoarthritis (OA) pathogenesis.
  • Peroxisome proliferator-activated receptor-γ (PPARγ) is a potential therapeutic target for OA.
  • This study investigates PPARγ's role in regulating AGEs-induced apoptosis and autophagy in human chondrocytes.

Purpose Of The Study

  • To investigate the molecular mechanisms by which PPARγ regulates AGEs-induced apoptosis and autophagy.
  • To determine the effect of PPARγ activation on MAPK and NF-κB signaling pathways in chondrocytes.
  • To evaluate pioglitazone as a potential therapeutic agent for OA.

Main Methods

  • Human chondrocytes were treated with AGEs, pioglitazone, and pathway inhibitors.
  • Apoptosis and autophagy were assessed using Western blot, TEM, and flow cytometry.
  • PPARγ, MAPK, NF-κB, MMP-13, and TNF-α levels were quantified.

Main Results

  • AGEs increased apoptosis, reduced autophagy, and activated MAPK/NF-κB pathways, downregulating PPARγ.
  • Pioglitazone and specific MAPK/NF-κB inhibitors restored autophagy and reduced apoptosis.
  • Pioglitazone and inhibitors decreased MMP-13 and TNF-α expression.

Conclusions

  • PPARγ activation mitigates AGEs-induced chondrocyte apoptosis and restores autophagy via MAPK/NF-κB regulation.
  • PPARγ agonism, exemplified by pioglitazone, offers a dual-target therapeutic strategy for OA.
  • Further clinical studies are warranted to confirm pioglitazone's efficacy in OA management.

Keywords:

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