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ATG5-mediated cGAS-STING-NLRP3 axis alleviates symptoms of knee osteoarthritis

  • 0Department of Sports Medicine, Yantaishan Hospital, No.10087 Science and Technology Avenue, Laishan District, Yantai, 264003, Shandong, China.
Human Cell +

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August 13, 2025

|

August 13, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

Autophagy-related protein 5 (ATG5) protects against knee osteoarthritis (KOA) by regulating the cGAS-STING-NLRP3 pathway. Enhancing ATG5 reduces inflammation and chondrocyte apoptosis, alleviating KOA progression.

Area Of Science

  • Biomedical Science
  • Molecular Biology
  • Immunology

Background

  • Knee osteoarthritis (KOA) involves cartilage degeneration and inflammation, driven by autophagy dysfunction.
  • The cGAS-STING-NLRP3 signaling pathway is implicated in KOA-related inflammation and apoptosis.

Purpose Of The Study

  • To investigate the regulatory role of autophagy-related protein 5 (ATG5) on the cGAS-STING-NLRP3 axis.
  • To elucidate the specific function of ATG5 in the pathogenesis of knee osteoarthritis.

Main Methods

  • Histological analysis (HE, Safranin O-fast green) and TUNEL staining in KOA rat models.
  • ELISA for inflammatory factors, Western blot and immunofluorescence for protein expression.
  • Flow cytometry for chondrocyte apoptosis assessment.

Main Results

  • KOA rats exhibited low ATG5 and high cGAS, STING, NLRP3 expression; ATG5 overexpression reduced inflammation and apoptosis markers.
  • ATG5 overexpression decreased Mankin scores and increased Beclin1, while ATG5 knockout reversed these effects.
  • Enhanced ATG5 expression protected chondrocytes by promoting autophagy and inhibiting inflammation, reducing KOA progression.

Conclusions

  • ATG5 modulates the cGAS-STING-NLRP3 axis to enhance chondrocyte autophagy.
  • ATG5 suppresses inflammation and apoptosis, thereby protecting chondrocytes.
  • ATG5 plays a protective role in knee osteoarthritis progression.

Keywords:

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