2. Academic Validation
  3. The glycolytic enzyme PFKFB3 alleviates DNA damage and chondrocyte senescence in osteoarthritis

The glycolytic enzyme PFKFB3 alleviates DNA damage and chondrocyte senescence in osteoarthritis

  • Cell Death Discov. 2025 Dec 8. doi: 10.1038/s41420-025-02903-0.
Bo Liu # 1,  Chenzhong Wang # 1,  Ziyu Weng 1,  Yi Yang 1,  Yi Shi 2 3,  Chi Zhang 4
Affiliations

Affiliations

  • 1 Department of Orthopedic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
  • 2 Department of Kidney Transplantation, Zhongshan Hospital, Fudan University, Shanghai, China. shi.yi@zs-hospital.sh.cn.
  • 3 Shanghai Key Laboratory of Organ Transplantation, Zhongshan Hospital, Fudan University, Shanghai, China. shi.yi@zs-hospital.sh.cn.
  • 4 Department of Orthopedic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China. zhang.chi@zs-hospital.sh.cn.
  • # Contributed equally.
PMID: 41360766 DOI: 10.1038/s41420-025-02903-0
Abstract

Chondrocyte senescence is a key driver of osteoarthritis (OA) progression. This study examined the role of the glycolytic enzyme PFKFB3 in regulating chondrocyte senescence during OA. Using a destabilization of the medial meniscus (DMM) mouse model, we found that PFKFB3 expression was reduced in human and mouse OA cartilage and in hydrogen peroxide-treated chondrocytes. PFKFB3 knockdown or overexpression in primary chondrocytes was achieved through RNA interference or lentiviral delivery, followed by RNA Sequencing and molecular analyses. PFKFB3 loss impaired DNA damage repair, activated NF-κB signaling, elevated pro-inflammatory cytokines, and promoted chondrocyte senescence, whereas PFKFB3 overexpression enhanced DNA repair and alleviated OA severity. Pharmacologic inhibition of NF-κB reduced inflammatory and senescent phenotypes in PFKFB3-deficient chondrocytes. These findings indicate that PFKFB3 regulates chondrocyte senescence via NF-κB signaling and DNA damage responses, suggesting PFKFB3 as a potential therapeutic target for OA.

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