{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T00:34:31Z","timestamp":1794011671471,"version":"4.8.0"},"reference-count":91,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,6,13]],"date-time":"2025-06-13T00:00:00Z","timestamp":1749772800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Apoptosis plays a crucial role in the progression of intervertebral disc degeneration (IVDD), a significant cause of chronic low back pain. This review explores disc cell apoptosis\u2019s cellular and molecular mechanisms, focusing on nucleus pulposus, annulus fibrosus, and cartilage endplates cells. Apoptotic pathways\u2014intrinsic (mitochondrial), extrinsic (death receptor-mediated), ER stress-mediated, and autophagy-related\u2014are activated by oxidative stress, inflammation, mechanical load, and metabolic disturbances like hyperglycemia. Diabetes exacerbates disc cell apoptosis through AGE-RAGE signaling and mitochondrial dysfunction. Inflammation further amplifies apoptotic cascades via cytokine signaling and ROS generation. The review also examines emerging therapeutic strategies, including antioxidants (e.g., MitoQ, resveratrol), anti-inflammatory agents (e.g., cytokine inhibitors), autophagy modulators (e.g., rapamycin, metformin), and stem cell and gene therapies. While promising preclinical results exist, challenges such as poor bioavailability and clinical translation remain. Enhanced understanding of apoptosis pathways informs future cellular preservation and matrix integrity treatments. Based on a comprehensive literature search from 2000 to 2025, this narrative review synthesizes current knowledge, identifies knowledge gaps, and discusses translational potential. Our findings support a paradigm shift toward mechanism-based therapies that address the root cause of IVDD rather than symptomatic relief alone.<\/jats:p>","DOI":"10.3390\/diagnostics15121510","type":"journal-article","created":{"date-parts":[[2025,6,13]],"date-time":"2025-06-13T09:51:24Z","timestamp":1749808284000},"page":"1510","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Apoptotic Pathway in Intervertebral Disc Degeneration: From Molecular Pathways to Clinical Interventions"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4237-4556","authenticated-orcid":false,"given":"Chae-Gwan","family":"Kong","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery, Uijeongbu St. Mary\u2019s Hospital, The Catholic University of Korea College of Medicine, Uijeongbu 11765, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8273-3731","authenticated-orcid":false,"given":"Jong-Beom","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Uijeongbu St. Mary\u2019s Hospital, The Catholic University of Korea College of Medicine, Uijeongbu 11765, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,13]]},"reference":[{"key":"ref_1","first-page":"59","article-title":"Overview of intervertebral disc degeneration: Pathophysiology, diagnosis, and treatment","volume":"10","author":"Feng","year":"2022","journal-title":"Bone Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1038\/s41584-020-00568-w","article-title":"Cell-based strategies for IVD repair: Clinical progress and translational obstacles","volume":"17","author":"Binch","year":"2021","journal-title":"Nat. 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