FGF9 Attenuates Osteoarthritis Progression Through The NRF2/GPX3 Antioxidant Axis

Description

In this episode of AI Talks with Bone & Joint, hosts Brian and Lisa discuss a June 2026 paper by YS Lo and colleagues titled 'FGF9 attenuates osteoarthritis progression through the NRF2/GPX3 antioxidant axis.' The conversation explains the motivation for the study, noting that osteoarthritis affects around 250 million people worldwide and remains difficult to treat with disease-modifying therapies. The researchers investigated the role of fibroblast growth factor 9 (FGF9) in chondrocyte degeneration and osteoarthritis pathogenesis using gene expression profiling, beta-galactosidase staining, flow cytometry, FGF9 knockdown experiments, FGF9-conditioned media, FGF9-enriched exosomes, and adenovirus-delivered FGF9 in a mouse model. The hosts highlight that FGF9 was downregulated in osteoarthritis chondrocytes, and that reducing FGF9 increased reactive oxygen species and cellular senescence by suppressing the NRF2/GPX3 antioxidant axis. In contrast, FGF9 promoted chondrogenesis, reduced senescence, and slowed osteoarthritis progression in mice. The episode also explains how NRF2 activates antioxidant genes such as GPX3 to reduce oxidative stress and preserve chondrocyte health. Brian describes how intra-articular FGF9 gene therapy in mice led to increased cartilage thickness and improved osteoarthritis scores, while FGF9-enriched exosomes reduced senescence in vitro. The discussion closes by noting the study’s limitations, including the need for further in vivo validation of safety and efficacy and additional exploration of related antioxidant enzymes and osteoarthritis models, while emphasizing the therapeutic promise of targeting the FGF9 pathway for osteoarthritis treatment.

Specialties

Paper Links

https://boneandjoint.org.uk/Article/10.1302/2046-3758.156.BJR-2025-0365.R1