{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T01:57:25Z","timestamp":1788832645997,"version":"build-2803163510"},"reference-count":129,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T00:00:00Z","timestamp":1766966400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004329","name":"Slovenian Research Agency","doi-asserted-by":"publisher","award":["J3-60058"],"award-info":[{"award-number":["J3-60058"]}],"id":[{"id":"10.13039\/501100004329","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Bioengineering"],"abstract":"<jats:p>This narrative review examines degenerative disc disease (DDD), a major cause of chronic back pain and disability worldwide. It is a multifactorial condition resulting from a complex interplay of genetic, mechanical, metabolic, and environmental factors that progressively impair disc structure and function. The pathophysiology of DDD involves disruption of extracellular matrix homeostasis, cellular senescence, oxidative stress, and chronic inflammation mediated by cytokines such as IL-1\u03b2, TNF-\u03b1, and IL-6. These processes are further modulated by signalling pathways including NF-\u03baB, MAPK, and Wnt\/\u03b2-catenin, leading to matrix degradation, dehydration, and loss of disc height. Epidemiological studies highlight the contribution of lifestyle and metabolic disorders, such as obesity, smoking, and diabetes, to disease progression. Traditional conservative and surgical treatments primarily alleviate symptoms but do not halt or reverse degeneration. In contrast, recent advances in molecular biology and regenerative medicine have opened new therapeutic avenues. Mesenchymal stem cell therapy, biomaterial scaffolds, and gene-based interventions aim to restore disc homeostasis by promoting matrix synthesis and suppressing catabolic activity. Despite promising experimental results, clinical translation remains limited by challenges in cell viability, delivery methods, and long-term efficacy. Future research integrating molecular, biomechanical, and regenerative strategies offers the potential for true biological repair and disc regeneration.<\/jats:p>","DOI":"10.3390\/bioengineering13010040","type":"journal-article","created":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T15:30:32Z","timestamp":1767195032000},"page":"40","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Degenerative Disease of Intervertebral Disc: A Narrative Review of Pathogenesis, Clinical Implications and Therapies"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3492-0297","authenticated-orcid":false,"given":"Lidija","family":"Gradisnik","sequence":"first","affiliation":[{"name":"Institute of Biomedical Sciences, Medical Faculty of Maribor, 2000 Maribor, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Kocivnik","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, University of Ljubljana, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2237-3786","authenticated-orcid":false,"given":"Uros","family":"Maver","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Sciences, Medical Faculty of Maribor, 2000 Maribor, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6283-4348","authenticated-orcid":false,"given":"Tomaz","family":"Velnar","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia"},{"name":"Faculty of Health Sciences, Alma Mater Europaea University, 2000 Maribor, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1007\/s00132-024-04578-4","article-title":"Biomechanik der Bandscheibe: Bedeutung degenerativer Ver\u00e4nderungen","volume":"53","author":"Welke","year":"2024","journal-title":"Die Orthop\u00e4die"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1007\/s40258-019-00471-w","article-title":"Systematic Review of Decision Analytic Modelling in Economic Evaluations of Low Back Pain and Sciatica","volume":"17","author":"Hall","year":"2019","journal-title":"Appl. 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