RICTOR-mediated GPX4 downregulation regulates chondrocyte ferroptosis in osteoarthritis progression

Area of Science:

• Biomedical Science
• Molecular Biology
• Cellular Biology

Background:

• Osteoarthritis (OA) is a prevalent degenerative joint disease causing pain and mobility loss.
• Ferroptosis is implicated in OA pathogenesis, but its mechanisms are not fully understood.
• RICTOR, a component of mTORC2, is known to regulate autophagy in OA.

Purpose of the Study:

• To investigate the role of RICTOR in chondrocyte ferroptosis.
• To explore the RICTOR-ferroptosis axis as a potential therapeutic target for OA.

Main Methods:

• Assessed RICTOR expression in OA patient cartilage and DMM mice.
• Utilized erastin-treated OA chondrocytes with RICTOR knockdown.
• Administered RICTOR inhibitor JR-AB2 in a DMM-induced OA mouse model.

Main Results:

• RICTOR expression was elevated in OA cartilage and DMM mice.
• RICTOR knockdown counteracted erastin effects on Col2a1 and MMP13.
• RICTOR inhibition reduced OA progression and GPX4 decline in vivo.

Conclusions:

• RICTOR promotes OA progression by inducing chondrocyte ferroptosis.
• RICTOR regulates ferroptosis through GPX4 expression.
• The RICTOR-ferroptosis pathway presents a potential therapeutic target for OA.