FBXW7 mediates intervertebral disc degeneration by regulating the JNK signaling pathway to induce nucleus pulposus cell apoptosis

Objective Elucidating the mechanistic role of FBXW7 in JNK pathway activation and subsequent nucleus pulposus apoptosis during disc degeneration. Background NPCs apoptosis constitutes a core pathological event during disc degeneration. Oxidative stress triggers JNK-mediated apoptotic signaling cascades in nucleus pulposus cells. As a core E3 ligase component, FBXW7 is involved in apoptosis regulation, but its role in NPCs apoptosis during IDD remains unexplored. Methods Bioinformatics analysis was performed on GEO datasets to identify differentially expressed genes in nucleus pulposus tissues of varying degeneration grades. Human NP samples with different degeneration levels were collected to assess FBXW7 expression. In vitro, NPCs were cultured, transfected with siRNA to silence FBXW7 or JNK, and subjected to apoptosis induction, followed by evaluation of apoptosis-related protein expression, cell apoptosis, and proliferation. In vivo IDD modeling employed rat disc puncture methodology, followed by local injection of FBXW7 shRNA to evaluate therapeutic effects on disc degeneration. Results FBXW7 and JNK expression were significantly upregulated in severely degenerated nucleus pulposus tissues. In vitro, FBXW7/JNK overexpression upregulated apoptotic effectors (Bax, Caspase-3) and downregulated Bcl-2, whereas FBXW7/JNK knockdown reduced apoptosis rates and mitigated TBHP-induced suppression of NPC proliferation. In vivo, FBXW7 shRNA injection delayed disc degeneration, attenuated T2-weighted MRI signal decline, and suppressed JNK expression. Conclusion FBXW7 and JNK are upregulated in advanced IDD. FBXW7 promotes NPCs apoptosis via the JNK pathway, and its knockdown alleviates disc degeneration progression in rats.