ArticleJournal of orthopaedic translation2025
Oxidative stress activates YAP/TEAD1/NCOA4 axis to promote ferroptosis of endplate chondrocytes and aggravate intervertebral disc degeneration.
Article in Journal of orthopaedic translation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- HIF-2α induces aggravated intervertebral disc degeneration by activating the IL-6/hepcidin-FPN1 axis and promoting ferroptosis in nucleus pulposus cells.Scientific reports · 2026Article
- Antioxidant Nanotherapies for Intervertebral Disk Degeneration: Progress and Prospects.Antioxidants (Basel, Switzerland) · 2026Review
- Ubiquitination in intervertebral disc degeneration: from mechanisms to potential therapeutic strategies.Journal of orthopaedic translation · 2026Review
- Macrophage-derived legumain ameliorates excessive mechanical stress-induced ferroptosis of nucleus pulposus cells and intervertebral disc degeneration via integrin αvβ3-Hippo signaling.Cellular & molecular biology letters · 2026Article
- The estrogen-ferroptosis axis in postmenopausal osteoporosis, osteoarthritis, and intervertebral disc degeneration: shared mechanisms and emerging evidence.Frontiers in immunology · 2026Review
- Tuina Analgesia Is Associated With the Modulation of the NCOA4-Mediated Ferroautophagy-Ferroptosis Pathway in SNL-Induced Neuropathic Pain Rats.Pain research & management · 2026Article
- Liuwei dihuang decoction attenuates intervertebral disc degeneration by inhibiting TRPA1-Mediated ferroptosis in endplate chondrocytes.Frontiers in cell and developmental biology · 2026Article
- Mechanotransduction in intervertebral disc degeneration: from compartment-specific sensors to translational frontiers.Frontiers in bioengineering and biotechnology · 2026Review
- From scientific discovery to orthopaedic clinical innovation.Journal of orthopaedic translation · 2025Article
- Mechanism-guided biomaterial strategies for intervertebral disc degeneration: Pathological heterogeneity, functional classification, and translational perspectives.Journal of tissue engineeringReview
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Authors and funding
10 authors.
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Abstract
Background: Intervertebral disc degeneration (IDD) is a major cause of low back pain, with cartilaginous endplate (CEP) degeneration playing a critical role. While Yes-associated protein (YAP) and its involvement in CEP degeneration and ferroptosis remain unclear. This study aimed to investigate the regulatory role of YAP in CEP ferroptosis and its underlying mechanisms. Methods: YAP expression was analyzed in human CEP tissues and mouse LSI models. CEP cells were treated with Verteporfin or YAP-siRNA. Ferroptosis was assessed by measuring iron levels, lipid peroxidation, GSH content, and viability assays. Molecular mechanisms were elucidated using CUT&RUN-qPCR, dual-LUC, and immunofluorescence colocalization. Verteporfin (VP) therapeutic efficacy was evaluated in LSI mice. Results: YAP knockdown attenuated oxidative stress-induced CEP chondrocyte degeneration and ferroptosis features. Mechanistically, we identified that oxidative stress-induced CEP chondrocyte degeneration involves ferritinophagy, which is regulated by the YAP/TEAD1 signaling axis through transcriptional control of nuclear coactivator 4 (NCOA4). Treatment with verteporfin, a YAP/TEAD1 axis inhibitor, effectively reduced CEP chondrocyte degeneration and IDD progression by targeting NCOA4-mediated ferritinophagy. Conclusion: Through detailed molecular and cellular analyses, we revealed that the YAP/TEAD1/NCOA4 signaling axis plays a crucial role in regulating CEP chondrocyte ferroptosis and IDD development. These findings not only enhance our understanding of IDD pathogenesis but also suggest that targeting the YAP/TEAD1/NCOA4 axis could be a promising therapeutic strategy for treating IDD. The Translational Potential of this Article: This study reveals YAP as a novel therapeutic target for intervertebral disc degeneration by regulating ferroptosis in cartilage endplate cells, which provides a novel strategy in the prevention of IDD.
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