Gradisnik L, Prestor B, Zele T, Kocivnik N, Maver U, Velnar T. Pathophysiology and current understanding of degenerative disc disease. World J Orthop 2026; 17(5): 117153 [DOI: 10.5312/wjo.v17.i5.117153]
Corresponding Author of This Article
Tomaz Velnar, Department of Neurosurgery, University Medical Centre Ljubljana, Zaloska 7, Ljubljana 1000, Slovenia. tvelnar@hotmail.com
Research Domain of This Article
Surgery
Article-Type of This Article
Review
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This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
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Gradisnik L, Prestor B, Zele T, Kocivnik N, Maver U, Velnar T. Pathophysiology and current understanding of degenerative disc disease. World J Orthop 2026; 17(5): 117153 [DOI: 10.5312/wjo.v17.i5.117153]
Lidija Gradisnik, Uros Maver, Institute of Biomedical Sciences, Faculty of Medicine, University of Maribor, Maribor 2000, Slovenia
Borut Prestor, Tilen Zele, Tomaz Velnar, Department of Neurosurgery, University Medical Centre Ljubljana, Ljubljana 1000, Slovenia
Tilen Zele, Tomaz Velnar, Alma Mater University Maribor, Maribor 2000, Slovenia
Nina Kocivnik, Faculty of Pharmacy, University of Ljubljana, Ljubljana 1000, Slovenia
Author contributions: Gradisnik L and Prestor B designed the research; Zele T and Kocivnik N analyzed the data; Gradisnik L and Velnar T wrote the paper; All authors contributed equally to this work and read and approved the final version of the manuscript.
AI contribution statement: The AI tool was used to check the English text before the submission of the article to the language editing services. We used the Instatext for the whole paper text. The article itself, otherwise, was written by the authors in the classic way and no AI was used during writing.
Supported by Slovenian Research Agency, No. J3-60058.
Conflict-of-interest statement: No conflicts of interest to disclose.
Corresponding author: Tomaz Velnar, Department of Neurosurgery, University Medical Centre Ljubljana, Zaloska 7, Ljubljana 1000, Slovenia. tvelnar@hotmail.com
Received: December 1, 2025 Revised: December 28, 2025 Accepted: February 12, 2026 Published online: May 18, 2026 Processing time: 169 Days and 22.8 Hours
Core Tip
Core Tip: Degenerative disc disease is a multifactorial condition caused by genetic, mechanical, metabolic, and environmental factors that disrupt disc homeostasis, resulting in chronic back pain and disability. Key pathological mechanisms include extracellular matrix degradation, oxidative stress, cellular senescence, and inflammation mediated by cytokines such as interleukin 1β, tumor necrosis factor-alpha, and interleukin 6 via several signaling pathways. While current treatments primarily address symptoms, emerging regenerative approaches, including mesenchymal stem cell therapy, biomaterial scaffolds, and gene-based interventions, aim to restore disc structure and function. Integrating molecular, biomechanical, and regenerative insights offers promise for achieving true biological disc repair.
