The Pivotal Role of Thioredoxin-Interacting Protein in Joint Degenerative Diseases
DOI:
https://doi.org/10.48048/tis.2025.9422Keywords:
TXNIP, Osteoarthritis, Intervertebral disc degeneration, Oxidative stress, InflammationAbstract
Thioredoxin-Interacting Protein (TXNIP) is a multifaceted protein that regulates oxidative stress (OS) and redox balance by inhibiting the antioxidant protein thioredoxin (TRX). TXNIP also activates the NOD-like receptor family, pyrin domain containing (NLRP3), promoting pro-inflammatory cytokines that exacerbate inflammation. Elevated TXNIP levels promote apoptosis in nucleus pulposus cells and chondrocytes, leading to accelerated tissue degeneration in intervertebral disc degeneration (IVDD) and osteoarthritis (OA) are articular degeneration diseases characterized by the degradation of cartilaginous tissues, primarily driven by oxidative stress, apoptosis, and extracellular matrix (ECM) remodeling. Recently, there has been a growing body of research focused on the mechanisms of TXNIP and its regulation in the OA and IVDD. Importantly, strategies that regulate TXNIP have demonstrated beneficial effects in preclinical experiments. Given the significance and novelty of TXNIP's role in articular degeneration diseases, we present an overview of its mechanisms and discuss its contributions to IVDD and OA. Additionally, we highlight the effectiveness of targeting TXNIP as a valuable strategy for improving our insight into and treatment of degenerative joint diseases.
HIGHLIGHTS
- Thioredoxin-Interacting Protein (TXNIP) inhibits the antioxidant protein thioredoxin (TRX), playing a vital role in regulating oxidative stress and redox balance.
- TXNIP activates the Nod-Like Receptor Protein3 (NLRP3) inflammasome, stimulating pro-inflammatory cytokines that worsen inflammation in joint tissues.
- Elevated levels of TXNIP result in apoptosis of nucleus pulposus cells and chondrocytes, contributing to tissue degeneration in intervertebral disc degeneration (IVDD) and osteoarthritis (OA).
- There is an increasing focus on the mechanisms of TXNIP in OA and IVDD, with promising approaches to modulate TXNIP demonstrating beneficial effects in preclinical studies.
- Targeting TXNIP is proposed as an important strategy for enhancing the understanding and treatment of degenerative joint diseases.
GRAPHICAL ABSTRACT
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