Resveratrol offers therapeutic potential in obesity-related osteoarthritis by targeting ferroptosis via G3BP1-SGs/mTOR modulation

  • Commun Biol. 2026 Jun 3. doi: 10.1038/s42003-026-10360-3.
Jianyi He  #  1  2  3 ,  Ze Li  #  1  2 ,  Haocheng Zhang  4 ,  Ye Yuan  1  2 ,  Ruiqi Wang  1  2 ,  Min Liu  1  2 ,  Qiwei Ma  1  2 ,  Hailun Gu  5 ,  Li Liu  6  7
Affiliations
  • 1. Key Laboratory of Environmental Stress and Chronic Disease Control & Prevention (China Medical University), Ministry of Education, Shenyang, PR China.
  • 2. Department of Nutrition and Food Hygiene, School of Public Health, China Medical University, Shenyang, PR China.
  • 3. Department of Clinical Nutrition, Jiangmen Central Hospital, Jiangmen, Guangdong, PR China.
  • 4. Capital Medical University, School of Basic Medical Sciences, Beijing, PR China.
  • 5. Department of Orthopedics, Shengjing Hospital of China Medical University, Shenyang, PR China. [email protected].
  • 6. Key Laboratory of Environmental Stress and Chronic Disease Control & Prevention (China Medical University), Ministry of Education, Shenyang, PR China. [email protected].
  • 7. Department of Nutrition and Food Hygiene, School of Public Health, China Medical University, Shenyang, PR China. [email protected].
  • # Contributed equally.
PMID: 42237016 DOI: 10.1038/s42003-026-10360-3
Abstract

The increased Ferroptosis by obesity contributes to the progression of osteoarthritis (OA). Resveratrol has protective effects against obesity-related OA. However, the underlying mechanisms remain unclear. Here, we investigated the mechanism of resveratrol against obesity-related OA using male C57BL/6 mice and chondrocyte models. The results demonstrated that high-fat diet (HFD) and IL-1β exacerbated cartilage damage in mice and chondrocytes, accompanied by worsening indicators of Ferroptosis and upregulation of Ras-GTPase-activating protein binding protein 1 (G3BP1) expression and stress granules (SGs) assembly, which responds to environmental stressors such as obesity. Resveratrol alleviated these effects. After G3BP1 was silenced, resveratrol no longer had the effect of inhibiting Ferroptosis and reducing cartilage degradation; while mTOR inhibition rescued ferroptosis-related protective proteins. This study suggests that resveratrol exerts protective effects against obesity-related OA, at least in part, by modulating ferroptosis-related changes in chondrocytes through the G3BP1-SGs/mTOR pathway. These findings provide new insights into OA pathogenesis and highlight resveratrol as a promising therapeutic strategy for obesity-related OA.

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