Publication Name	World Journal of Orthopedics
Manuscript ID	117153
Country	Slovenia

Category	Surgery
Manuscript Type	Review
Article Title	Pathophysiology and current understanding of degenerative disc disease: A brief review
Manuscript Source	Invited Manuscript
All Author List	Lidija Gradisnik, Borut Prestor, Tilen Zele, Nina Kocivnik, Uros Maver and Tomaz Velnar
Funding Agency and Grant Number	Funding Agency Grant Number Slovenian Research Agency No. J3-60058
Corresponding Author	Tomaz Velnar, Department of Neurosurgery, University Medical Centre Ljubljana, Zaloska 7, Ljubljana 1000, Slovenia. tvelnar@hotmail.com
Key Words	Intervertebral disc; Degenerative disc disease; Degeneration; Cytokines; Cellular senescence; Treatment
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 (IL)-1β, tumor necrosis factor-alpha, and IL-6 via NF-κB, MAPK, and Wnt/β-catenin signalling 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.
Citation	Gradisnik L, Prestor B, Zele T, Kocivnik N, Maver U, Velnar T. Pathophysiology and current understanding of degenerative disc disease: A brief review. World J Orthop 2026; In press

Received	2025-12-01 01:49
Peer-Review Started	2025-12-02 03:28
First Decision by Editorial Office Director	2025-12-23 10:24
Return for Revision	2025-12-23 10:24
Revised	2025-12-28 19:34
Publication Fee Transferred
Second Decision by Editor	2026-02-12 02:44
Second Decision by Editor-in-Chief
Final Decision by Editorial Office Director	2026-02-12 08:16
Articles in Press	2026-02-12 08:16
Edit the Manuscript by Language Editor
Typeset the Manuscript

ISSN	2218-5836 (online)
Open Access	This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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: https://creativecommons.org/Licenses/by-nc/4.0/
Copyright	The Author(s) 2026. Published by Baishideng Publishing Group Inc. All rights reserved.
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