Fibroblast growth factor 9 reduces TBHP-induced oxidative stress in chondrocytes and diminishes mouse osteoarthritis...

Area of Science:

• Biochemistry
• Cell Biology
• Orthopedics

Background:

• Osteoarthritis (OA) is a degenerative joint disease driven by oxidative stress, chondrocyte apoptosis, and mitochondrial dysfunction.
• Fibroblast growth factor 9 (FGF9) exhibits antioxidant properties and influences degenerative diseases through ERK signaling.
• The precise role of FGF9 in OA pathogenesis, particularly its antioxidant mechanisms, remains incompletely understood.

Purpose of the Study:

• To elucidate the mechanism by which FGF9 affects osteoarthritis.
• To investigate the association between FGF9, oxidative stress, and related signaling pathways in OA.
• To evaluate the therapeutic potential of FGF9 in OA models.

Main Methods:

• In vivo study using destabilization of the medial meniscus (DMM) mouse model for OA.
• In vitro study using tert-butyl hydroperoxide (TBHP)-induced chondrocytes to mimic oxidative stress.
• Analysis of chondrocyte apoptosis, mitochondrial function, and signaling pathway activation (ERK, Nrf2/HO1).

Main Results:

• FGF9 treatment decreased oxidative stress, apoptosis, and mitochondrial dysfunction in TBHP-induced chondrocytes.
• FGF9 promoted Nrf2 nuclear translocation, activating the Nrf2/HO1 signaling pathway.
• Inhibition of Nrf2 or ERK signaling abrogated FGF9's antioxidant effects.
• FGF9 administration ameliorated joint space narrowing, cartilage ossification, and synovial thickening in DMM mice.

Conclusions:

• FGF9 inhibits oxidative stress in chondrocytes through the ERK and Nrf2-HO1 signaling pathways.
• FGF9 demonstrates a protective effect against osteoarthritis progression in vivo.
• FGF9 represents a potential therapeutic agent for osteoarthritis treatment.