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Updated: Jun 5, 2026
Software-Assisted Quantitative Measurement of Osteoarthritic Subchondral Bone Thickness
Published on: March 18, 2022
FGF9 attenuates osteoarthritis progression through the NRF2/GPX3 antioxidant axis
Yuan-Shun Lo1,2,3, Tsung-Ming Chen4, Teng-Le Huang5,6
1Department of Orthopedic Surgery, China Medical University Beigang Hospital, China Medical University, Yunlin, Taiwan.
Aims:
Osteoarthritis (OA), a prevalent age-related joint disease affecting over 250 million people globally, currently lacks effective disease-modifying treatments. Fibroblast growth factor 9 (FGF9) has shown cartilage-protective effects in post-traumatic OA models, but its role in chondrocyte degeneration and OA pathogenesis remains unclear. This study investigates FGF9's function in human and murine chondrocytes and its therapeutic potential for OA.
Methods:
Gene expression profiling was performed on primary chondrocytes from OA patients and normal controls. Senescence and reactive oxygen species (ROS) levels were assessed by β-galactosidase staining and flow cytometry. FGF9 function was evaluated through short hairpin RNA (shRNA)-mediated knockdown and treatment with FGF9-conditioned media (CM). The impact of FGF9-enriched exosomes on chondrocyte senescence was also examined in vitro. In vivo effects were tested using adenovirus-delivered FGF9 in a destabilization of the medial meniscus (DMM)-induced OA mouse model.
Results:
FGF9 expression was significantly downregulated in OA chondrocytes (n = 195) compared to normal (n = 71). FGF9 knockdown elevated ROS levels and senescence via suppression of the NRF2/GPX3 antioxidant axis, while FGF9 promoted chondrogenesis in mesenchymal stem cells. Intra-articular FGF9 gene therapy reduced OA progression in DMM mice. Additionally, FGF9-enriched exosomes reduced senescence in primary chondrocytes in vitro.
Conclusion:
FGF9 alleviates OA progression by activating the NRF2/GPX3 pathway, reducing ROS and chondrocyte senescence. These findings support the therapeutic potential of FGF9 and FGF9-enriched exosomes in OA treatment.
Insights
Fibroblast growth factor 9 (FGF9) protects cartilage by reducing oxidative stress and chondrocyte aging in osteoarthritis (OA). FGF9 therapy, including gene therapy and exosomes, shows promise for treating OA progression.
Area of Science:
- Biochemistry
- Cell Biology
- Orthopedics
Background:
- Osteoarthritis (OA) is a widespread degenerative joint disease with limited treatment options.
- Fibroblast growth factor 9 (FGF9) has demonstrated cartilage protection, but its precise role in OA pathogenesis is not fully understood.
Purpose of the Study:
- To investigate the function of FGF9 in human and murine chondrocytes.
- To evaluate the therapeutic potential of FGF9 and FGF9-derived exosomes for OA treatment.
Main Methods:
- Gene expression profiling of OA and normal chondrocytes.
- Assessment of chondrocyte senescence and reactive oxygen species (ROS) levels.
- In vitro and in vivo studies using FGF9 knockdown, FGF9-conditioned media, FGF9-enriched exosomes, and adenovirus-mediated FGF9 gene therapy in an OA mouse model.
Main Results:
- FGF9 expression is downregulated in OA chondrocytes.
- FGF9 suppression increases ROS and senescence by inhibiting the NRF2/GPX3 antioxidant pathway.
- FGF9 promotes chondrogenesis and reduces OA progression in vivo.
- FGF9-enriched exosomes decrease chondrocyte senescence.
Conclusions:
- FGF9 alleviates OA progression by activating the NRF2/GPX3 pathway, reducing ROS and chondrocyte senescence.
- FGF9 and FGF9-enriched exosomes represent potential therapeutic strategies for osteoarthritis.
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