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Updated: Jan 9, 2026
Software-Assisted Quantitative Measurement of Osteoarthritic Subchondral Bone Thickness
Published on: March 18, 2022
The glycolytic enzyme PFKFB3 alleviates DNA damage and chondrocyte senescence in osteoarthritis
Bo Liu1, Chenzhong Wang1, Ziyu Weng1
1Department of Orthopedic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
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.
Insights
Phosphofructobase-1-kinase/fructose-biphosphatase 3 (PFKFB3) deficiency accelerates osteoarthritis by impairing DNA repair and promoting inflammation. Restoring PFKFB3 alleviates disease severity, highlighting its therapeutic potential.
Area of Science:
- Biochemistry
- Cell Biology
- Rheumatology
Background:
- Chondrocyte senescence is a critical factor in osteoarthritis (OA) pathogenesis.
- The role of specific metabolic enzymes in chondrocyte senescence and OA progression remains incompletely understood.
Purpose of the Study:
- To investigate the function of the glycolytic enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) in chondrocyte senescence and OA.
- To determine if PFKFB3 influences OA severity through NF-κB signaling and DNA damage responses.
Main Methods:
- Utilized a destabilization of the medial meniscus (DMM) mouse model of osteoarthritis.
- Manipulated PFKFB3 expression in primary chondrocytes using RNA interference and lentiviral vectors.
- Performed RNA sequencing and molecular analyses to assess signaling pathways and cellular phenotypes.
- Investigated the effect of pharmacologic NF-κB inhibition.
Main Results:
- PFKFB3 expression was decreased in human and mouse OA cartilage and in vitro stressed chondrocytes.
- PFKFB3 deficiency led to impaired DNA damage repair, activated NF-κB signaling, increased pro-inflammatory cytokines, and enhanced chondrocyte senescence.
- PFKFB3 overexpression improved DNA repair and reduced OA severity.
- NF-κB inhibition ameliorated the inflammatory and senescent phenotypes in PFKFB3-deficient chondrocytes.
Conclusions:
- PFKFB3 plays a crucial role in regulating chondrocyte senescence during osteoarthritis progression.
- PFKFB3 acts through modulation of NF-κB signaling and DNA damage repair pathways.
- PFKFB3 represents a promising therapeutic target for the treatment of osteoarthritis.
