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

Authors

Xuening Liu, Fengguang Yang, Yanni Duan, Hefang Xiao, Zhenyu Cao, Zhaoheng Wang, Haijun Zhang, Xuewen Kang

Published in

Cell proliferation. Pages e70256. Jul 14, 2026. Epub Jul 14, 2026.

Abstract

Excessive mechanical stress is a main cause of intervertebral disc degeneration (IDD). However, the specific mechanism remains unclear. We established in vivo and in vitro models to investigate the role of cytoskeletal proteins in excessive mechanical stress-induced NP cell pyroptosis and IDD. The expression level of Vimentin was decreased in degenerated NP cells induced by excessive mechanical stress. Knockdown of Vimentin promoted NP cell pyroptosis and IDD in rats, whereas Vimentin overexpression significantly alleviated excessive mechanical stress-induced NP cell pyroptosis and degeneration. Further mechanistic studies revealed that Vimentin ameliorated mitochondrial dysfunction triggered by excessive mechanical stress through PINK1-Parkin-dependent mitophagy, thereby attenuating NP cell pyroptosis and degeneration. Co-immunoprecipitation-mass spectrometry analysis suggested an interaction between Itgb1 and Vimentin, which was validated by Co-immunoprecipitation assays. Itgb1 enhanced Vimentin protein stability via the ubiquitin-proteasome pathway and inhibited mechanical stress-mediated Vimentin degradation. Subsequent experiments confirmed that Itgb1 reduced Vimentin ubiquitination and degradation by blocking the binding of MNAT1 to Vimentin. Itgb1 ameliorated excessive mechanical stress-induced NP cell pyroptosis and degeneration via Vimentin. Restoring Vimentin function through gene overexpression effectively inhibited NP cell pyroptosis and delayed the progression of IDD in rats. In summary, this study reveals a mechanotransduction pathway from mechanical stress sensing to cellular functional regulation in IDD, providing novel insights into the pathological mechanisms underlying IDD. Moreover, this study demonstrates that Vimentin exerts a significant protective effect against excessive mechanical stress-induced NP cell pyroptosis and IDD, offering a potential therapeutic target for the clinical management of IDD.

PMID:
42446500
Bibliographic data and abstract were imported from PubMed on 14 Jul 2026.

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