Itgb1-Mediated Stabilization of Vimentin Alleviates Excessive Mechanical Stress-Induced Nucleus Pulposus Cell Pyroptosis and Intervertebral Disc Degeneration via PINK1-Parkin-Dependent Mitophagy

This study investigated how excessive mechanical stress contributes to intervertebral disc degeneration by focusing on nucleus pulposus cell pyroptosis, cytoskeletal regulation, and mitochondrial quality control. The authors analyzed human nucleus pulposus tissues with different degeneration grades, used a rat tail compression suture model of intervertebral disc degeneration, and compressed primary rat nucleus pulposus cells in vitro. Excessive mechanical stress increased pyroptosis markers including NLRP3, GSDMD, and IL-1β, disrupted extracellular matrix metabolism, and reduced Vimentin expression. Vimentin knockdown worsened nucleus pulposus cell pyroptosis, matrix degradation, disc height loss, and degeneration in rats, while Vimentin overexpression reduced compression-induced pyroptosis and extracellular matrix imbalance. Mechanistically, Vimentin improved mitochondrial function and reduced reactive oxygen species by supporting PINK1-Parkin-dependent mitophagy. The study also identified Itgb1 as a Vimentin-interacting protein that stabilizes Vimentin through the ubiquitin-proteasome pathway by limiting MNAT1-mediated Vimentin ubiquitination. Itgb1 overexpression reduced compression-induced mitophagy impairment, pyroptosis, and matrix catabolism through Vimentin. Overall, the study presents an Itgb1-Vimentin-PINK1/Parkin mechanotransduction pathway that protects nucleus pulposus cells from excessive mechanical stress and may offer therapeutic targets for intervertebral disc degeneration.