Journal of Shanghai Jiao Tong University (Medical Science) >

2026 , Vol. 46 >Issue 5: 568 - 575

DOI: https://doi.org/10.3969/j.issn.1674-8115.2026.05.002

Frontier review

Thioredoxin-interacting protein: a potential novel therapeutic target for intervertebral disc degeneration

  • Liu Yadong ,
  • Dong Jinwei ,
  • Wang Zihui ,
  • Lü Zekun ,
  • Ding Baozhi ,
  • Ma Hui
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  • 1.Second Clinical Medical College, Yunnan University of Chinese Medicine, Kunming 650500, China
    2.Department of Orthopedics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201999, China
    3.Shanghai Key Laboratory of Orthopedic Implants, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
    4.Department of Orthopedics, Affiliated Renhe Hospital of Shanghai University, Shanghai 200431, China
Ma Hui, E-mail: sh9_spine@163.com.

Received date: 2025-09-28

  Accepted date: 2026-02-06

  Online published: 2026-05-15

Supported by

Natural Science Foundation of Shanghai(23ZR1447400);Scientific Research Foundation of Education Department of Yunnan Province of China(2025Y0641)

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Abstract

The identification of biomarkers is essential for developing innovative therapeutic strategies for intervertebral disc degeneration (IVDD). Thioredoxin-interacting protein (TXNIP), a member of the α-arrestin protein family, is modulated by various cellular stress responses and inhibits the antioxidant activity of thioredoxin through direct binding, thereby promoting oxidative stress. Furthermore, TXNIP interacts with nucleotide-binding domain-like receptor protein 3 (NLRP3) to directly activate inflammatory pathways, playing a pivotal role in IVDD progression. IVDD is a common degenerative disorder closely associated with aging, oxidative stress, and chronic inflammation. Currently, there are no effective drugs to reverse its progression. Recent studies have shown that, in degenerated intervertebral discs, TXNIP expression level is closely associated with inflammatory factors, oxidative damage, and cell death, indicating that TXNIP may serve as a central molecular node linking multiple pathological mechanisms in IVDD. This review systematically elucidates the biological functions of TXNIP in oxidative stress, inflammatory activation, metabolic reprogramming, pyroptosis, and apoptosis, as well as its regulatory networks, and summarizes its pivotal role in the occurrence and development of IVDD. Furthermore, from a translational medicine perspective, this review summarizes the current research progress of therapeutic strategies targeting TXNIP, including small-molecule inhibitors, natural compounds, genetic interventions, and biomaterials, and proposes a multimodal therapeutic pathway and clinical translation direction targeting TXNIP, aiming to provide new insights and theoretical foundations for the mechanistic research and targeted treatment of IVDD.

Key words： thioredoxin-interacting protein (TXNIP); intervertebral disc degeneration (IVDD); targeted therapy

Cite this article

Liu Yadong , Dong Jinwei , Wang Zihui , Lü Zekun , Ding Baozhi , Ma Hui . Thioredoxin-interacting protein: a potential novel therapeutic target for intervertebral disc degeneration[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2026 , 46(5) : 568 -575 . DOI: 10.3969/j.issn.1674-8115.2026.05.002

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