2. Academic Validation
  3. Eicosapentaenoic acid restores inflammation-induced changes in chondrocyte mechanics by suppressing the NF-κB p65/CD44 signaling pathway and attenuates osteoarthritis

Eicosapentaenoic acid restores inflammation-induced changes in chondrocyte mechanics by suppressing the NF-κB p65/CD44 signaling pathway and attenuates osteoarthritis

  • Exp Mol Med. 2025 Sep;57(9):1963-1977. doi: 10.1038/s12276-025-01529-7.
Qihao Yang # 1 2,  Jianqun Wu # 3,  Songqiang Huang # 4,  Jing Zeng # 5,  Yihan Jing 1,  Zhiyong Wang 1,  Chi Zhang 1,  Zenghui Wu 1,  Song Liu 6,  Zhao Wang 7
Affiliations

Affiliations

  • 1 Department of Orthopaedic Surgery, Guangzhou Key laboratory of Spine Disease Prevention and Treatment, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.
  • 2 Department of Pain, Hubei No. 3 People's Hospital of Jianghan University, Wuhan, China.
  • 3 Department of Traumatic Surgery, Center for Orthopaedic Surgery, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China.
  • 4 School of Biomedical Sciences, Hunan University, Changsha, China.
  • 5 Department of Orthopedics, Liwan Central Hospital of Guangzhou, Guangzhou, China.
  • 6 Department of Orthopaedic Surgery, Guangzhou Key laboratory of Spine Disease Prevention and Treatment, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, China. Ispine@163.com.
  • 7 Department of Orthopaedic Surgery, Guangzhou Key laboratory of Spine Disease Prevention and Treatment, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, China. z.wang@gzhmu.edu.cn.
  • # Contributed equally.
PMID: 40887495 DOI: 10.1038/s12276-025-01529-7
Abstract

Here we investigate the effects and mechanisms of eicosapentaenoic acid (EPA) in regulating chondrocyte mechanics during inflammation in the progression of osteoarthritis (OA). Primary porcine chondrocytes and human OA chondrocytes were isolated and cultured. Cell mechanical properties were measured using atomic force microscopy. RNA Sequencing, immunocytochemistry, quantitative PCR and western blotting were used to elucidate associated signaling mechanisms. Porcine cartilage and human OA cartilage explants were collected. Human articular cartilage samples were obtained from ten donors. Anterior cruciate ligament transection surgery was performed to induce OA in male C57BL/6J mice. The therapeutic effects of EPA and activation of associated signaling were evaluated using histology, immunohistochemistry and micro-computed tomography. EPA reduced F-actin intensity and Young's modulus in IL-1α-treated porcine chondrocytes and in human OA chondrocytes. Mechanistically, EPA inhibited IL-1α-induced increase in CD44 expression in porcine chondrocytes by suppressing phosphorylation of NF-κB subunits p65. In addition, EPA alleviated articular cartilage degeneration and decreased the expression of p-p65 and CD44 in IL-1α-treated porcine and human OA cartilage explants. Moreover, EPA suppressed the increase in Young's modulus induced by CD44 ligands (A6 peptide and low-molecular-weight hyaluronic acid) in porcine chondrocytes. Finally, intraarticular injection of EPA emulsion-integrated hyaluronic acid injection attenuated OA-associated alterations in articular cartilage and subchondral bone and decreased CD44 expression in mice. Our data not only provide new insights into EPA's chondroprotective actions and underlying mechanisms but also offer new evidence supporting the therapeutic efficacy of a novel EPA emulsion-integrated hyaluronic acid injection for OA treatment.

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