Calming sterile inflammation in intervertebral disc degeneration: taurine disrupts mitochondria-cGAS-STING signaling via autophagy enhancement

Abstract

Background: Intervertebral disc degeneration (IVDD) is a major pathological process leading to low back pain, closely associated with the functional decline of nucleus pulposus progenitor cell (NPPC). The role of the cGAS-STING pathway in mediating DNA-sensing-associated inflammation and senescence in IVDD has not been fully elucidated.

Methods: This study integrated genetics, computational biology, cellular experiments, and animal models to systematically investigate whether taurine (TAU) exerts protective effects by modulating this pathway.

Results: Mendelian randomization analysis suggested a causal relationship between higher TAU levels and reduced risk of IVDD. Molecular docking and dynamics simulations demonstrated that TAU stably binds to cGAS and STING. In both degenerated human nucleus pulposus (NP) tissues and an H₂O₂-induced NPPC senescence model, the cGAS-STING pathway was significantly activated. TAU intervention maintained mitochondrial function, reduced cytosolic mtDNA leakage, and enhanced autophagic degradation of STING, thereby suppressing downstream TBK1-IRF3/NLRP3 inflammatory signaling and subsequently alleviating cellular senescence, inflammatory responses, and apoptosis. TAU treatment effectively delayed intervertebral disc height loss, histopathological progression, and pain sensitivity in a rat IVDD model.

Conclusion: This study is the first to reveal that TAU mitigates IVDD through multi-targeted modulation of the “mitochondria-cGAS-STING” axis, providing a theoretical foundation for its translational application as a disease-modifying agent.

Keywords

taurine / intervertebral disc degeneration / STING / mitochondria / nucleus pulposus progenitor cell

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