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Updated: Jun 7, 2025

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Inhibition of PA28γ expression can alleviate osteoarthritis by inhibiting endoplasmic reticulum stress and promoting

Haokun Mo1, Kai Sun1, Yanjun Hou1

  • 1Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Bone & Joint Research
|November 20, 2024
PubMed
Abstract

Insights

PA28γ knockdown in chondrocytes reduces osteoarthritis progression by inhibiting inflammation, apoptosis, and endoplasmic reticulum stress. This approach also promotes STAT3 phosphorylation, offering a potential therapeutic strategy for osteoarthritis.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Orthopedics

Background:

  • Osteoarthritis (OA) is a prevalent degenerative joint disease characterized by cartilage breakdown.
  • PA28γ, a proteasome activator, influences cellular processes like apoptosis and inflammation, suggesting a role in OA pathogenesis.

Purpose of the Study:

  • To investigate the role of PA28γ in osteoarthritis development and its underlying mechanisms.
  • To explore the impact of PA28γ on chondrocyte endoplasmic reticulum (ER) stress and associated signaling pathways.

Main Methods:

  • Primary chondrocytes were isolated from mice and treated to assess PA28γ effects on OA indicators.
  • Western blotting, real-time PCR, and immunofluorescence were used to study PA28γ in ER stress.
  • An OA mouse model was created using destabilized medial meniscus (DMM) surgery, with PA28γ expression reduced via adenovirus injection.

Main Results:

  • PA28γ knockdown improved chondrocyte anabolism/catabolism, inhibited inflammation, apoptosis, and ER stress.
  • PA28γ knockdown modulated IRE1α phosphorylation and TRAF2 expression, impacting MAPK and NF-κB pathways.
  • PA28γ knockdown promoted STAT3 phosphorylation, reducing ER stress, while its inhibition exacerbated ER stress. Cartilage destruction was reduced in vivo.

Conclusions:

  • PA28γ knockdown mitigates OA by inhibiting chondrocyte anabolic/catabolic dysregulation, inflammation, and apoptosis.
  • PA28γ knockdown suppresses ER stress in chondrocytes through enhanced STAT3 phosphorylation, presenting a potential therapeutic target for OA.

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