{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T23:26:06Z","timestamp":1793489166365,"version":"4.5.0"},"reference-count":198,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T00:00:00Z","timestamp":1779321600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>With the global population aging, intervertebral disc degeneration (IDD), an aging-related disease, has been confirmed to be an important cause of low back pain (LBP). LBP can affect people of all ages and has now become one of the leading noncommunicable diseases, resulting in reduced life expectancy and functional disability in patients. Previous studies have mostly focused on the effects of factors such as mechanical load and genetics on intervertebral disc degeneration. With the deepening of research, the focus has gradually shifted to metabolic disorders, among which lipid metabolism plays a non-negligible role. Lipid metabolism is involved in the construction of cell structure and microenvironment, which is crucial for maintaining normal physiological functions. Abnormal levels of free fatty acids, triglycerides, and cholesterol are widely recognized as risk factors for intervertebral disc degeneration. Lipid metabolism disorders participate in the pathological process of intervertebral disc degeneration through the following pathways: affecting the release of pro-inflammatory cytokines, activating oxidative stress, inducing excessive autophagy, and triggering endoplasmic reticulum stress. Meanwhile, these four pathways can synergistically exacerbate intervertebral disc degeneration. This paper reviews studies on the association between lipid metabolism disorders and intervertebral disc degeneration, focusing on the underlying pathological mechanisms, so as to provide new insights for further exploring the treatment and intervention strategies of intervertebral disc degeneration, and emphasizes the significance of lipid metabolism in maintaining intervertebral disc health.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1843872","type":"journal-article","created":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T04:52:34Z","timestamp":1779339154000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Revisiting intervertebral disc degeneration: lipid metabolism disorders as overlooked contributors to complex pathology"],"prefix":"10.3389","volume":"17","author":[{"given":"Shuang","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Orthopedics, First Affiliated Hospital of Dalian Medical University","place":["Dalian, Liaoning, China"]},{"name":"Key Laboratory of Molecular Mechanism for Repair and Remodeling of Orthopedic Diseases","place":["Dalian, Liaoning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongshan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, First Affiliated Hospital of Dalian Medical University","place":["Dalian, Liaoning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaizhong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, First Affiliated Hospital of Dalian Medical University","place":["Dalian, Liaoning, China"]},{"name":"Key Laboratory of Molecular Mechanism for Repair and Remodeling of Orthopedic Diseases","place":["Dalian, Liaoning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, First Affiliated Hospital of Dalian Medical University","place":["Dalian, Liaoning, China"]},{"name":"Key Laboratory of Molecular Mechanism for Repair and Remodeling of Orthopedic Diseases","place":["Dalian, Liaoning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anqiao","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, First Affiliated Hospital of Dalian Medical University","place":["Dalian, Liaoning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moran","family":"Suo","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, First Affiliated Hospital of Dalian Medical University","place":["Dalian, Liaoning, China"]},{"name":"Key Laboratory of Molecular Mechanism for Repair and Remodeling of Orthopedic Diseases","place":["Dalian, Liaoning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, First Affiliated Hospital of Dalian Medical University","place":["Dalian, Liaoning, China"]},{"name":"Key Laboratory of Molecular Mechanism for Repair and Remodeling of Orthopedic Diseases","place":["Dalian, Liaoning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhonghai","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, First Affiliated Hospital of Dalian Medical University","place":["Dalian, Liaoning, China"]},{"name":"Key Laboratory of Molecular Mechanism for Repair and Remodeling of Orthopedic Diseases","place":["Dalian, Liaoning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1093\/neuros\/nyw078","article-title":"Intervertebral disk degeneration and repair","volume":"80","author":"Dowdell","year":"2017","journal-title":"Neurosurgery"},{"key":"B2","doi-asserted-by":"publisher","first-page":"27","DOI":"10.7150\/thno.48987","article-title":"Small molecule-based treatment approaches for intervertebral disc degeneration: Current options and future directions","volume":"11","author":"Kamali","year":"2021","journal-title":"Theranostics"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(99)01312-4","article-title":"Epidemiological features of chronic low-back pain","volume":"354","author":"Andersson","year":"1999","journal-title":"Lancet"},{"key":"B4","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1007\/978-3-319-99124-5_138","article-title":"Low back pain","volume":"398","author":"Knezevic","year":"2021","journal-title":"Lancet"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(24)00757-8","article-title":"Global incidence, prevalence, years lived with disability (YLDs), disability-adjusted life-years (DALYs), and healthy life expectancy (HALE) for 371 diseases and injuries in 204 countries and territories and 811 subnational locations, 1990-2021: a systematic analysis for the Global Burden of Disease Study 2021","volume":"403","author":"Diseases","year":"2024","journal-title":"Lancet"},{"key":"B6","doi-asserted-by":"publisher","first-page":"398","DOI":"10.1016\/j.joca.2015.09.019","article-title":"Aging and age related stresses: a senescence mechanism of intervertebral disc degeneration","volume":"24","author":"Wang","year":"2016","journal-title":"Osteoarthritis Cartilage"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2007.08.001","article-title":"The cell biology of intervertebral disc aging and degeneration","volume":"6","author":"Zhao","year":"2007","journal-title":"Ageing Res Rev"},{"key":"B8","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1093\/rheumatology\/ken396","article-title":"The cellular pathobiology of the degenerate intervertebral disc and discogenic back pain","volume":"48","author":"Freemont","year":"2009","journal-title":"Rheumatol (Oxford)"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2024.102294","article-title":"Lipids and lipid metabolism in cellular senescence: Emerging targets for age-related diseases","volume":"97","author":"Zeng","year":"2024","journal-title":"Ageing Res Rev"},{"key":"B10","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1186\/s12944-021-01450-8","article-title":"Prevalence of plasma lipid disorders with an emphasis on LDL cholesterol in selected countries in the Asia-Pacific region","volume":"20","author":"Lee","year":"2021","journal-title":"Lipids Health Dis"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3390\/medsci6020034","article-title":"The role of adipokines in intervertebral disc degeneration","volume":"6","author":"Sharma","year":"2018","journal-title":"Med Sci (Basel)"},{"key":"B12","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1038\/nri2921","article-title":"Adipokines in inflammation and metabolic disease","volume":"11","author":"Ouchi","year":"2011","journal-title":"Nat Rev Immunol"},{"key":"B13","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1038\/nrrheum.2016.49","article-title":"Adipokines in bone disease","volume":"12","author":"Neumann","year":"2016","journal-title":"Nat Rev Rheumatol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1097\/ede.0b013e3181f20808","article-title":"Associations between serum lipid levels and chronic low back pain","volume":"21","author":"Heuch","year":"2010","journal-title":"Epidemiology"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0147565","article-title":"Metabolic syndrome components are associated with intervertebral disc degeneration: The Wakayama Spine Study","volume":"11","author":"Teraguchi","year":"2016","journal-title":"PloS One"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22010375","article-title":"Intervertebral disc and adipokine leptin-loves me, loves me not","volume":"22","author":"Curic","year":"2020","journal-title":"Int J Mol Sci"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2019.01284","article-title":"Obesity mediates apoptosis and extracellular matrix metabolic imbalances via MAPK pathway activation in intervertebral disk degeneration","volume":"10","author":"Zhang","year":"2019","journal-title":"Front Physiol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.803132","article-title":"Cholesterol induces pyroptosis and matrix degradation via mSREBP1-driven endoplasmic reticulum stress in intervertebral disc degeneration","volume":"9","author":"Yan","year":"2021","journal-title":"Front Cell Dev Biol"},{"key":"B19","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1186\/s10020-024-00887-8","article-title":"Dysregulated lipid metabolism and intervertebral disc degeneration: the important role of ox-LDL\/LOX-1 in endplate chondrocyte senescence and calcification","volume":"30","author":"Bing","year":"2024","journal-title":"Mol Med"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2023.101902","article-title":"Epigenetic modifications of inflammation in intervertebral disc degeneration","volume":"87","author":"Kang","year":"2023","journal-title":"Ageing Res Rev"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1002\/ar.1092200402","article-title":"Human intervertebral disc: structure and function","volume":"220","author":"Humzah","year":"1988","journal-title":"Anat Rec"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.7150\/thno.33638","article-title":"Exosomes from mesenchymal stem cells modulate endoplasmic reticulum stress to protect against nucleus pulposus cell death and ameliorate intervertebral disc degeneration in vivo","volume":"9","author":"Liao","year":"2019","journal-title":"Theranostics"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2015.03.028","article-title":"Mechanics and biology in intervertebral disc degeneration: a vicious circle","volume":"23","author":"Vergroesen","year":"2015","journal-title":"Osteoarthritis Cartilage"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.30039","article-title":"Involvement of oxidative stress-induced annulus fibrosus cell and nucleus pulposus cell ferroptosis in intervertebral disc degeneration pathogenesis","volume":"236","author":"Yang","year":"2021","journal-title":"J Cell Physiol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2023.1259731","article-title":"Recent advances in the repair of degenerative intervertebral disc for preclinical applications","volume":"11","author":"Ying","year":"2023","journal-title":"Front Bioeng Biotechnol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1097\/00007632-199005000-00011","article-title":"Investigation of the laminate structure of lumbar disc anulus fibrosus","volume":"15","author":"Marchand","year":"1990","journal-title":"Spine (Phila Pa 1976)"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1002\/art.27444","article-title":"Proinflammatory cytokine expression profile in degenerated and herniated human intervertebral disc tissues","volume":"62","author":"Shamji","year":"2010","journal-title":"Arthritis Rheum"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.18632\/aging.102266","article-title":"Impact of NF-\u03baB pathway on the apoptosis-inflammation-autophagy crosstalk in human degenerative nucleus pulposus cells","volume":"11","author":"Yi","year":"2019","journal-title":"Aging (Albany NY)"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2020.03.018","article-title":"Extracellular matrix in vascular disease, part 2\/4: JACC focus seminar","volume":"75","author":"Barallobre-Barreiro","year":"2020","journal-title":"J Am Coll Cardiol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1007\/s10495-013-0839-1","article-title":"Cell death in intervertebral disc degeneration","volume":"18","author":"Ding","year":"2013","journal-title":"Apoptosis"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.prp.2021.153366","article-title":"Role of the Wnt pathway in the formation, development, and degeneration of intervertebral discs","volume":"220","author":"Wu","year":"2021","journal-title":"Pathol Res Pract"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.202500228","article-title":"A biomimetic silk fibroin\/chitosan membrane for annulus fibrosus sealing to prevent intervertebral disc re-herniation","volume":"14","author":"Lu","year":"2025","journal-title":"Adv Healthc Mater"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2021-0091tr","article-title":"Basement membrane extracellular matrix proteins in pulmonary vascular and right ventricular remodeling in pulmonary hypertension","volume":"65","author":"Ambade","year":"2021","journal-title":"Am J Respir Cell Mol Biol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2024.102323","article-title":"The role of oxidative stress in intervertebral disc degeneration: Mechanisms and therapeutic implications","volume":"98","author":"Chen","year":"2024","journal-title":"Ageing Res Rev"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1042\/bst0350652","article-title":"Matrix synthesis and degradation in human intervertebral disc degeneration","volume":"35","author":"Le Maitre","year":"2007","journal-title":"Biochem Soc Trans"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21103601","article-title":"MicroRNAs in intervertebral disc degeneration, apoptosis, inflammation, and mechanobiology","volume":"21","author":"Cazzanelli","year":"2020","journal-title":"Int J Mol Sci"},{"key":"B37","doi-asserted-by":"publisher","first-page":"1221","DOI":"10.3892\/etm.2021.10655","article-title":"Roles of circular RNAs in the pathogenesis of intervertebral disc degeneration (Review)","volume":"22","author":"Lin","year":"2021","journal-title":"Exp Ther Med"},{"key":"B38","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1186\/s10020-025-01220-7","article-title":"STMN1-IGFBP5 axis induces senescence and extracellular matrix degradation in nucleus pulposus cells: In vivo and in vitro insights","volume":"31","author":"Li","year":"2025","journal-title":"Mol Med"},{"key":"B39","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1186\/s13075-023-03028-4","article-title":"TAK-715 alleviated IL-1\u03b2-induced apoptosis and ECM degradation in nucleus pulposus cells and attenuated intervertebral disc degeneration ex vivo and in vivo","volume":"25","author":"Wang","year":"2023","journal-title":"Arthritis Res Ther"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2024.1489420","article-title":"From structure to therapy: the critical influence of cartilaginous endplates and microvascular network on intervertebral disc degeneration","volume":"12","author":"Sun","year":"2024","journal-title":"Front Bioeng Biotechnol"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1016\/j.mtbio.2024.101081","article-title":"A natural hydrogel complex improves intervertebral disc degeneration by correcting fatty acid metabolism and inhibiting nucleus pulposus cell pyroptosis","volume":"26","author":"Wang","year":"2024","journal-title":"Mater Today Bio"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.7554\/elife.54693","article-title":"Senotherapeutic drugs for human intervertebral disc degeneration and low back pain","volume":"9","author":"Cherif","year":"2020","journal-title":"Elife"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1186\/ar4274","article-title":"Hyaluronic acid fragments enhance the inflammatory and catabolic response in human intervertebral disc cells through modulation of toll-like receptor 2 signalling pathways","volume":"15","author":"Quero","year":"2013","journal-title":"Arthritis Res Ther"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1093\/neuros\/nyx149","article-title":"The role of hypoxia in angiogenesis and extracellular matrix regulation of intervertebral disc cells during inflammatory reactions","volume":"81","author":"Kwon","year":"2017","journal-title":"Neurosurgery"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1097\/00007632-200206150-00007","article-title":"Increased nerve and blood vessel ingrowth associated with proteoglycan depletion in an ovine anular lesion model of experimental disc degeneration","volume":"27","author":"Melrose","year":"2002","journal-title":"Spine (Phila Pa 1976)"},{"key":"B46","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1038\/nrrheum.2013.160","article-title":"Role of cytokines in intervertebral disc degeneration: pain and disc content","volume":"10","author":"Risbud","year":"2014","journal-title":"Nat Rev Rheumatol"},{"key":"B47","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1186\/s12967-016-0833-9","article-title":"IL-17 mediates inflammatory reactions via p38\/c-Fos and JNK\/c-Jun activation in an AP-1-dependent manner in human nucleus pulposus cells","volume":"14","author":"Li","year":"2016","journal-title":"J Transl Med"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2015.04.060","article-title":"Lipoxin A4 attenuates radicular pain possibly by inhibiting spinal ERK, JNK and NF-kappaB\/p65 and cytokine signals, but not p38, in a rat model of non-compressive lumbar disc herniation","volume":"300","author":"Miao","year":"2015","journal-title":"Neuroscience"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2025.1533264","article-title":"Lipid metabolic disorders and their impact on cartilage endplate and nucleus pulposus function in intervertebral disk degeneration","volume":"12","author":"Wu","year":"2025","journal-title":"Front Nutr"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1097\/brs.0b013e3181f72b94","article-title":"Human disc nucleus properties and vertebral endplate permeability","volume":"36","author":"Rodriguez","year":"2011","journal-title":"Spine"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1097\/00007632-199602150-00003","article-title":"Transport properties of the human cartilage endplate in relation to its composition and calcification","volume":"21","author":"Roberts","year":"1996","journal-title":"Spine"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1267\/ahc.37.109","article-title":"Herniated and spondylotic intervertebral discs of the human cervical spine: Histological and immunohistochemical observations","volume":"37","author":"Kokubo","year":"2004","journal-title":"Acta Histochem Cytochem"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.2174\/1389201024666221021142904","article-title":"Pathomechanism of the IVDs degeneration and the role of neurotrophic factors and concentration of selected elements in genesis of low back pain","volume":"24","author":"Staszkiewicz","year":"2023","journal-title":"Curr Pharm Bio\/Technol"},{"key":"B54","doi-asserted-by":"publisher","first-page":"7403","DOI":"10.1038\/s41598-017-07780-x","article-title":"Possible involvement of the oxLDL\/LOX-1 system in the pathogenesis and progression of human intervertebral disc degeneration or herniation","volume":"7","author":"Li","year":"2017","journal-title":"Sci Rep"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.r066514","article-title":"Lipid signaling and lipotoxicity in metaflammation: Indications for metabolic disease pathogenesis and treatment","volume":"57","author":"Ertunc","year":"2016","journal-title":"J Lipid Res"},{"key":"B56","doi-asserted-by":"publisher","first-page":"100994","DOI":"10.1016\/j.jlr.2026.100994","article-title":"An integrative approach to studying sphingolipid metabolism reveals p53 as a master regulator of the pathway","volume":"67","author":"Ghandour","year":"2026","journal-title":"J Lipid Res"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.3390\/biom11121873","article-title":"Essential fatty acids and their metabolites in the pathobiology of inflammation and its resolution","volume":"11","author":"Das","year":"2021","journal-title":"Biomolecules"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.5507\/bp.2011.038","article-title":"Fatty acids as biocompounds: Their role in human metabolism, health and disease--a review. Part 1: Classification, dietary sources and biological functions","volume":"155","author":"Tvrzicka","year":"2011","journal-title":"BioMed Pap Med Fac Univ Palacky Olomouc Czech Repub"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2015.04.060","article-title":"Lipoxin A4 attenuates radicular pain possibly by inhibiting spinal ERK, JNK and NF-\u03baB\/p65 and cytokine signals, but not p38, in a rat model of non-compressive lumbar disc herniation","volume":"300","author":"Miao","year":"2015","journal-title":"Neuroscience"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.14389","article-title":"Epoxyeicosanoids prevent intervertebral disc degeneration in vitro and in vivo","volume":"8","author":"Li","year":"2017","journal-title":"Oncotarget"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.18632\/aging.205674","article-title":"Relationship between fatty acid intake and aging: A Mendelian randomization study","volume":"16","author":"Chen","year":"2024","journal-title":"Aging (Albany NY)"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.3390\/nu10040432","article-title":"Obesity, inflammation, Toll-like receptor 4 and fatty acids","volume":"10","author":"Rogero","year":"2018","journal-title":"Nutrients"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1080\/10408398.2013.842887","article-title":"The role of dietary cholesterol in lipoprotein metabolism and related metabolic abnormalities: A mini-review","volume":"56","author":"Kapourchali","year":"2016","journal-title":"Crit Rev Food Sci Nutr"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1172\/jci0216381","article-title":"Cholesterol in health and disease","volume":"110","author":"Tabas","year":"2002","journal-title":"J Clin Invest"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20082030","article-title":"Molecular relationships among obesity, inflammation and intervertebral disc degeneration: Are adipokines the common link","volume":"20","author":"Ruiz-Fernandez","year":"2019","journal-title":"Int J Mol Sci"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2019.00069","article-title":"The unique metabolic characteristics of bone marrow adipose tissue","volume":"10","author":"Li","year":"2019","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1038\/nri1937","article-title":"Adipocytokines: Mediators linking adipose tissue, inflammation and immunity","volume":"6","author":"Tilg","year":"2006","journal-title":"Nat Rev Immunol"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1080\/21623945.2021.1910155","article-title":"Visfatin promotes intervertebral disc degeneration by inducing IL-6 expression through the ERK\/JNK\/p38 signalling pathways","volume":"10","author":"Cui","year":"2021","journal-title":"Adipocyte"},{"key":"B69","doi-asserted-by":"publisher","first-page":"8936","DOI":"10.21203\/rs.3.rs-646684\/v1","article-title":"Adipokine human resistin promotes obesity-associated inflammatory intervertebral disc degeneration via pro-inflammatory cytokine cascade activation","volume":"12","author":"Shin","year":"2022","journal-title":"Sci Rep"},{"key":"B70","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/j.arr.2014.12.001","article-title":"Aging and dyslipidemia: A review of potential mechanisms","volume":"19","author":"Liu","year":"2015","journal-title":"Ageing Res Rev"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.17392\/1698-23","article-title":"Histopathological spectrum of lumbar disc changes in obesity: Analysis of intervertebral discs in lumbar hernia patients in Zenica-Doboj Canton, Bosnia and Herzegovina","volume":"21","author":"Jukovic-Bihorac","year":"2024","journal-title":"Med Glas (Zenica)"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.2106\/jbjs.i.01568","article-title":"A population-based study of juvenile disc degeneration and its association with overweight and obesity, low back pain, and diminished functional status","volume":"93","author":"Samartzis","year":"2011","journal-title":"J Bone Joint Surg Am"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1016\/j.spinee.2015.02.001","article-title":"The relationship between obesity, low back pain, and lumbar disc degeneration when genetics and the environment are considered: A systematic review of twin studies","volume":"15","author":"Dario","year":"2015","journal-title":"Spine J"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2021.740200","article-title":"Causal associations of obesity with the intervertebral degeneration, low back pain, and sciatica: A two-sample Mendelian randomization study","volume":"12","author":"Zhou","year":"2021","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2015-007805","article-title":"Role of overweight and obesity in low back disorders among men: A longitudinal study with a life course approach","volume":"5","author":"Frilander","year":"2015","journal-title":"BMJ Open"},{"key":"B76","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1038\/s41584-021-00713-z","article-title":"A new immunometabolic perspective of intervertebral disc degeneration","volume":"18","author":"Francisco","year":"2022","journal-title":"Nat Rev Rheumatol"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1007\/s00586-011-1737-2","article-title":"Symptomatic disc herniation and serum lipid levels","volume":"20","author":"Longo","year":"2011","journal-title":"Eur Spine J"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1016\/j.jos.2018.08.006","article-title":"Effect of hyperlipidaemia to accelerate intervertebral disc degeneration in the injured rat caudal disc model","volume":"24","author":"Zhang","year":"2019","journal-title":"J Orthop Sci"},{"key":"B79","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1186\/s12944-016-0248-x","article-title":"Serum lipid levels are positively correlated with lumbar disc herniation--a retrospective study of 790 Chinese patients","volume":"15","author":"Zhang","year":"2016","journal-title":"Lipids Health Dis"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2022.1033375","article-title":"Impact of dyslipidemia on the severity of symptomatic lumbar spine degeneration: A retrospective clinical study","volume":"9","author":"Huang","year":"2022","journal-title":"Front Nutr"},{"key":"B81","doi-asserted-by":"publisher","first-page":"1302","DOI":"10.1186\/s12889-023-16224-3","article-title":"The impact of dyslipidemia on lumbar intervertebral disc degeneration and vertebral endplate modic changes: A cross-sectional study of 1035 citizens in China","volume":"23","author":"Yuan","year":"2023","journal-title":"BMC Public Health"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2474-9-24","article-title":"Degeneration of the intervertebral disc","volume":"5","author":"Urban","year":"2003","journal-title":"Arthritis Res Ther"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ijo.0802974","article-title":"Disc degeneration of the lumbar spine in relation to overweight","volume":"29","author":"Liuke","year":"2005","journal-title":"Int J Obes (Lond)"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1007\/s00586-018-5778-7","article-title":"Leptin and the intervertebral disc: A biochemical link exists between obesity, intervertebral disc degeneration and low back pain-an in vitro study in a bovine model","volume":"28","author":"Segar","year":"2019","journal-title":"Eur Spine J"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2026.116294","article-title":"Lipid metabolism: A molecular switch to control inflammation","volume":"173","author":"Cheng","year":"2026","journal-title":"Int Immunopharmacol"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2025.124092","article-title":"The adipokine Isthmin-1 in obesity and its complications: Recent research advances","volume":"384","author":"Zhuang","year":"2026","journal-title":"Life Sci"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbspin.2017.09.010","article-title":"Vertebral marrow adipose tissue adipokines as a possible cause of intervertebral disc inflammation","volume":"85","author":"Vrselja","year":"2018","journal-title":"Joint Bone Spine"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2018.00640","article-title":"Obesity, fat mass and immune system: Role for leptin","volume":"9","author":"Francisco","year":"2018","journal-title":"Front Physiol"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26199819","article-title":"Cinnamaldehyde inhibits leptin-induced MMP-1 by modulating leptin receptor\/STAT3 and blocking RhoA\/NF-\u03baB pathways in human intervertebral disc stem cells","volume":"26","author":"Hua","year":"2025","journal-title":"Int J Mol Sci"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.1097\/brs.0b013e31818338e5","article-title":"Expression of leptin and its functional receptor on disc cells: Contribution to cell proliferation","volume":"33","author":"Zhao","year":"2008","journal-title":"Spine (Phila Pa 1976)"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.3390\/ijms15011176","article-title":"Leptin activates RhoA\/ROCK pathway to induce cytoskeleton remodeling in nucleus pulposus cells","volume":"15","author":"Li","year":"2014","journal-title":"Int J Mol Sci"},{"key":"B92","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2015.3646","article-title":"Leptin modulates the expression of catabolic genes in rat nucleus pulposus cells through the mitogen-activated protein kinase and Janus kinase 2\/signal transducer and activator of transcription 3 pathways","volume":"12","author":"Miao","year":"2015","journal-title":"Mol Med Rep"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24108566","article-title":"Anti-inflammatory effects of adiponectin receptor agonist AdipoRon against intervertebral disc degeneration","volume":"24","author":"Ohnishi","year":"2023","journal-title":"Int J Mol Sci"},{"key":"B94","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1186\/s13018-016-0481-z","article-title":"Expression of adiponectin receptors in human and rat intervertebral disc cells and changes in receptor expression during disc degeneration using a rat tail temporary static compression model","volume":"11","author":"Terashima","year":"2016","journal-title":"J Orthop Surg Res"},{"key":"B95","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2014.1909","article-title":"Association of adiponectin protein and ADIPOQ gene variants with lumbar disc degeneration","volume":"8","author":"Khabour","year":"2014","journal-title":"Exp Ther Med"},{"key":"B96","doi-asserted-by":"publisher","DOI":"10.1097\/brs.0000000000002364","article-title":"Adiponectin downregulates TNF-alpha expression in degenerated intervertebral discs","volume":"43","author":"Yuan","year":"2018","journal-title":"Spine (Phila Pa 1976)"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.1002\/jsp2.70040","article-title":"Low-frequency cyclic stretch upregulates the expression of nuclear factor erythroid 2-related factor 2 in human nucleus pulposus cells to inhibit the resistin-induced interleukin-20 expression","volume":"8","author":"Yen","year":"2025","journal-title":"JOR Spine"},{"key":"B98","doi-asserted-by":"publisher","DOI":"10.1038\/35053000","article-title":"The hormone resistin links obesity to diabetes","volume":"409","author":"Steppan","year":"2001","journal-title":"Nature"},{"key":"B99","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/s1043-2760(01)00522-7","article-title":"Resistin and obesity-associated insulin resistance","volume":"13","author":"Steppan","year":"2002","journal-title":"Trends Endocrinol Metab"},{"key":"B100","doi-asserted-by":"publisher","DOI":"10.2174\/1381612819666131206103102","article-title":"Resistin: An inflammatory cytokine. Role in cardiovascular diseases, diabetes and the metabolic syndrome","volume":"20","author":"Abate","year":"2014","journal-title":"Curr Pharm Des"},{"key":"B101","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2016.10.002","article-title":"Resistin promotes CCL4 expression through toll-like receptor-4 and activation of the p38-MAPK and NF-kappaB signaling pathways: implications for intervertebral disc degeneration","volume":"25","author":"Li","year":"2017","journal-title":"Osteoarthritis Cartilage"},{"key":"B102","doi-asserted-by":"publisher","DOI":"10.3390\/cells9112444","article-title":"Visfatin: A possible role in cardiovasculo-metabolic disorders","volume":"9","author":"Dakroub","year":"2020","journal-title":"Cells"},{"key":"B103","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2015.117","article-title":"Physiological and pathophysiological roles of NAMPT and NAD metabolism","volume":"11","author":"Garten","year":"2015","journal-title":"Nat Rev Endocrinol"},{"key":"B104","doi-asserted-by":"publisher","first-page":"796","DOI":"10.1007\/s10753-019-01166-z","article-title":"Nicotinamide phosphoribosyl transferase controls NLRP3 inflammasome activity through MAPK and NF-kappaB signaling in nucleus pulposus cells, as suppressed by melatonin","volume":"43","author":"Huang","year":"2020","journal-title":"Inflammation"},{"key":"B105","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1042\/bj3180001","article-title":"The lipocalin protein family: structure and function","volume":"318","author":"Flower","year":"1996","journal-title":"Biochem J"},{"key":"B106","doi-asserted-by":"publisher","DOI":"10.1002\/hep.27853","article-title":"Resminostat: Opening the door to epigenetic treatments for liver cancer","volume":"63","author":"Zhao","year":"2016","journal-title":"Hepatology"},{"key":"B107","doi-asserted-by":"publisher","DOI":"10.1021\/pr049772a","article-title":"Quantitative proteomic analysis of the secretory proteins from rat adipose cells using a 2D liquid chromatography-MS\/MS approach","volume":"4","author":"Chen","year":"2005","journal-title":"J Proteome Res"},{"key":"B108","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0096997","article-title":"Lipocalin 2 expression and secretion is highly regulated by metabolic stress, cytokines, and nutrients in adipocytes","volume":"9","author":"Zhang","year":"2014","journal-title":"PloS One"},{"key":"B109","doi-asserted-by":"publisher","DOI":"10.1002\/ctm2.70370","article-title":"Single nuclear-spatial transcriptomic sequencing reveals distinct puncture-induced cell subpopulations in the intervertebral disc of a rat model","volume":"15","author":"Liang","year":"2025","journal-title":"Clin Transl Med"},{"key":"B110","doi-asserted-by":"publisher","DOI":"10.1210\/me.2007-0420","article-title":"The role of lipocalin 2 in the regulation of inflammation in adipocytes and macrophages","volume":"22","author":"Zhang","year":"2008","journal-title":"Mol Endocrinol"},{"key":"B111","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1186\/s12951-024-02556-8","article-title":"M1 macrophage-derived exosomes promote intervertebral disc degeneration by enhancing nucleus pulposus cell senescence through LCN2\/NF-kappaB signaling axis","volume":"22","author":"Fan","year":"2024","journal-title":"J Nanobiotechnology"},{"key":"B112","doi-asserted-by":"publisher","DOI":"10.1007\/s00586-014-3675-2","article-title":"Nerve growth factor increases MMP9 activity in annulus fibrosus cells by upregulating lipocalin 2 expression","volume":"24","author":"Kao","year":"2015","journal-title":"Eur Spine J"},{"key":"B113","doi-asserted-by":"publisher","DOI":"10.3171\/2014.6.spine13756","article-title":"Nerve growth factor promotes expression of novel genes in intervertebral disc cells that regulate tissue degradation: Laboratory investigation","volume":"21","author":"Kao","year":"2014","journal-title":"J Neurosurg Spine"},{"key":"B114","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.m608744200","article-title":"Cartilage oligomeric matrix protein associates with granulin-epithelin precursor (GEP) and potentiates GEP-stimulated chondrocyte proliferation","volume":"282","author":"Xu","year":"2007","journal-title":"J Biol Chem"},{"key":"B115","doi-asserted-by":"publisher","DOI":"10.1212\/nxi.0000000000001133","article-title":"Progranulin suppressed autoimmune uveitis and autoimmune neuroinflammation by inhibiting Th1\/Th17 cells and promoting Treg cells and M2 macrophages","volume":"9","author":"Wang","year":"2022","journal-title":"Neurol Neuroimmunol Neuroinflamm"},{"key":"B116","doi-asserted-by":"publisher","DOI":"10.1002\/art.27491","article-title":"Granulin-epithelin precursor binds directly to ADAMTS-7 and ADAMTS-12 and inhibits their degradation of cartilage oligomeric matrix protein","volume":"62","author":"Guo","year":"2010","journal-title":"Arthritis Rheum"},{"key":"B117","doi-asserted-by":"publisher","DOI":"10.2741\/4234","article-title":"The role of PGRN in musculoskeletal development and disease","volume":"19","author":"Konopka","year":"2014","journal-title":"Front Biosci (Landmark Ed)"},{"key":"B118","doi-asserted-by":"publisher","DOI":"10.1007\/s10753-018-0828-1","article-title":"Progranulin is positively associated with intervertebral disc degeneration by interaction with IL-10 and IL-17 through TNF pathways","volume":"41","author":"Wang","year":"2018","journal-title":"Inflammation"},{"key":"B119","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.22766","article-title":"Progranulin derived engineered protein Atsttrin suppresses TNF-\u03b1-mediated inflammation in intervertebral disc degenerative disease","volume":"8","author":"Ding","year":"2017","journal-title":"Oncotarget"},{"key":"B120","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.cell.2018.09.048","article-title":"Biological functions of autophagy genes: A disease perspective","volume":"176","author":"Levine","year":"2019","journal-title":"Cell"},{"key":"B121","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.cell.2007.12.018","article-title":"Autophagy in the pathogenesis of disease","volume":"132","author":"Levine","year":"2008","journal-title":"Cell"},{"key":"B122","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1146\/annurev.nutr.27.061406.093749","article-title":"Protein turnover via autophagy: implications for metabolism","volume":"27","author":"Mizushima","year":"2007","journal-title":"Annu Rev Nutr"},{"key":"B123","doi-asserted-by":"publisher","DOI":"10.7150\/thno.49860","article-title":"Selective autophagy of intracellular organelles: recent research advances","volume":"11","author":"Li","year":"2021","journal-title":"Theranostics"},{"key":"B124","doi-asserted-by":"publisher","first-page":"91","DOI":"10.2147\/jir.s434896","article-title":"Role of autophagy and pyroptosis in intervertebral disc degeneration","volume":"17","author":"Wang","year":"2024","journal-title":"J Inflammation Res"},{"key":"B125","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.13903","article-title":"Melatonin protects vertebral endplate chondrocytes against apoptosis and calcification via the Sirt1-autophagy pathway","volume":"23","author":"Zhang","year":"2019","journal-title":"J Cell Mol Med"},{"key":"B126","doi-asserted-by":"publisher","DOI":"10.1002\/jsp2.1286","article-title":"Impact of autophagy inhibition on intervertebral disc cells and extracellular matrix","volume":"7","author":"Kritschil","year":"2024","journal-title":"JOR Spine"},{"key":"B127","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2021.119266","article-title":"Autophagy as a potential therapeutic target in intervertebral disc degeneration","volume":"273","author":"Gong","year":"2021","journal-title":"Life Sci"},{"key":"B128","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.29129","article-title":"lncRNA HOTAIR upregulates autophagy to promote apoptosis and senescence of nucleus pulposus cells","volume":"235","author":"Zhan","year":"2020","journal-title":"J Cell Physiol"},{"key":"B129","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2013.10.002","article-title":"Autophagy is activated in compression-induced cell degeneration and is mediated by reactive oxygen species in nucleus pulposus cells exposed to compression","volume":"21","author":"Ma","year":"2013","journal-title":"Osteoarthritis Cartilage"},{"key":"B130","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-021-00650-7","article-title":"Mitochondrial quality control in intervertebral disc degeneration","volume":"53","author":"Song","year":"2021","journal-title":"Exp Mol Med"},{"key":"B131","doi-asserted-by":"publisher","DOI":"10.1007\/s10495-012-0708-3","article-title":"Role of mitochondrial pathway in compression-induced apoptosis of nucleus pulposus cells","volume":"17","author":"Ding","year":"2012","journal-title":"Apoptosis"},{"key":"B132","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2022.2162245","article-title":"The mitophagy receptor BNIP3 is critical for the regulation of metabolic homeostasis and mitochondrial function in the nucleus pulposus cells of the intervertebral disc","volume":"19","author":"Madhu","year":"2023","journal-title":"Autophagy"},{"key":"B133","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s12276-019-0331-2","article-title":"Mitochondrial NDUFA4L2 attenuates the apoptosis of nucleus pulposus cells induced by oxidative stress via the inhibition of mitophagy","volume":"51","author":"Xu","year":"2019","journal-title":"Exp Mol Med"},{"key":"B134","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2023.2274205","article-title":"The NLRX1-SLC39A7 complex orchestrates mitochondrial dynamics and mitophagy to rejuvenate intervertebral disc by modulating mitochondrial Zn(2+) trafficking","volume":"20","author":"Song","year":"2024","journal-title":"Autophagy"},{"key":"B135","doi-asserted-by":"publisher","DOI":"10.1007\/s00264-013-2037-8","article-title":"High glucose-induced oxidative stress promotes autophagy through mitochondrial damage in rat notochordal cells","volume":"37","author":"Park","year":"2013","journal-title":"Int Orthop"},{"key":"B136","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.2019.4212","article-title":"Autophagy protects nucleus pulposus cells from cyclic mechanical tension-induced apoptosis","volume":"44","author":"Yang","year":"2019","journal-title":"Int J Mol Med"},{"key":"B137","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1186\/s13075-022-02804-y","article-title":"Excessive mechanical stress-induced intervertebral disc degeneration is related to Piezo1 overexpression triggering the imbalance of autophagy\/apoptosis in human nucleus pulpous","volume":"24","author":"Shi","year":"2022","journal-title":"Arthritis Res Ther"},{"key":"B138","doi-asserted-by":"publisher","DOI":"10.1080\/03008207.2020.1736578","article-title":"Compression stress induces nucleus pulposus cell autophagy by inhibition of the PI3K\/AKT\/mTOR pathway and activation of the JNK pathway","volume":"62","author":"Li","year":"2021","journal-title":"Connect Tissue Res"},{"key":"B139","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.29097","article-title":"TIGAR impedes compression-induced intervertebral disc degeneration by suppressing nucleus pulposus cell apoptosis and autophagy","volume":"235","author":"Li","year":"2020","journal-title":"J Cell Physiol"},{"key":"B140","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1038\/s41419-022-04593-3","article-title":"The regulation, function, and role of lipophagy, a form of selective autophagy, in metabolic disorders","volume":"13","author":"Zhang","year":"2022","journal-title":"Cell Death Dis"},{"key":"B141","doi-asserted-by":"publisher","DOI":"10.1038\/s41569-023-00885-z","article-title":"A role for lipophagy in atherosclerosis","volume":"20","author":"Laval","year":"2023","journal-title":"Nat Rev Cardiol"},{"key":"B142","doi-asserted-by":"publisher","first-page":"690","DOI":"10.1080\/15548627.2020.1728097","article-title":"Lipophagy-derived fatty acids undergo extracellular efflux via lysosomal exocytosis","volume":"17","author":"Cui","year":"2021","journal-title":"Autophagy"},{"key":"B143","doi-asserted-by":"publisher","DOI":"10.1093\/procel\/pwac063","article-title":"ORP8 acts as a lipophagy receptor to mediate lipid droplet turnover","volume":"14","author":"Pu","year":"2023","journal-title":"Protein Cell"},{"key":"B144","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2022.03.022","article-title":"Ferroptosis at the intersection of lipid metabolism and cellular signaling","volume":"82","author":"Liang","year":"2022","journal-title":"Mol Cell"},{"key":"B145","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2011.03.023","article-title":"Autophagy regulates cholesterol efflux from macrophage foam cells via lysosomal acid lipase","volume":"13","author":"Ouimet","year":"2011","journal-title":"Cell Metab"},{"key":"B146","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2022.116643","article-title":"Hyperlipidemia impacts osteogenesis via lipophagy","volume":"167","author":"Ji","year":"2023","journal-title":"Bone"},{"key":"B147","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.2016.2564","article-title":"Plumbagin exerts protective effects in nucleus pulposus cells by attenuating hydrogen peroxide-induced oxidative stress, inflammation and apoptosis through NF-kappaB and Nrf-2","volume":"37","author":"Chu","year":"2016","journal-title":"Int J Mol Med"},{"key":"B148","doi-asserted-by":"publisher","DOI":"10.1016\/j.mad.2004.07.009","article-title":"The role of oxidative damage and stress in aging","volume":"125","author":"Bokov","year":"2004","journal-title":"Mech Ageing Dev"},{"key":"B149","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2025.1662845","article-title":"Elemental imbalance and oxidative biomarker shifts in lumbar disc degeneration","volume":"16","author":"Strojny","year":"2025","journal-title":"Front Neurol"},{"key":"B150","doi-asserted-by":"publisher","DOI":"10.1097\/00007632-199705150-00003","article-title":"Toward a biochemical understanding of human intervertebral disc degeneration and herniation. Contributions of nitric oxide, interleukins, prostaglandin E2, and matrix metalloproteinases","volume":"22","author":"Kang","year":"1997","journal-title":"Spine (Phila Pa 1976)"},{"key":"B151","doi-asserted-by":"publisher","DOI":"10.1111\/obr.12670","article-title":"Mast cells participate in chronic low-grade inflammation within adipose tissue","volume":"19","author":"Zelechowska","year":"2018","journal-title":"Obes Rev"},{"key":"B152","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2023.114711","article-title":"Cellular senescence - molecular mechanisms of intervertebral disc degeneration from an immune perspective","volume":"162","author":"Song","year":"2023","journal-title":"BioMed Pharmacother"},{"key":"B153","doi-asserted-by":"publisher","DOI":"10.1002\/jor.22320","article-title":"Mitochondrial-derived reactive oxygen species (ROS) play a causal role in aging-related intervertebral disc degeneration","volume":"31","author":"Nasto","year":"2013","journal-title":"J Orthop Res"},{"key":"B154","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/b978-0-12-822778-7.00021-3","article-title":"Tumor necrosis factor-alpha: a key contributor to intervertebral disc degeneration","volume":"49","author":"Wang","year":"2017","journal-title":"Acta Biochim Biophys Sin (Shanghai)"},{"key":"B155","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/2240894","article-title":"Hydroxytyrosol ameliorates intervertebral disc degeneration and neuropathic pain by reducing oxidative stress and inflammation","volume":"2022","author":"Yu","year":"2022","journal-title":"Oxid Med Cell Longev"},{"key":"B156","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2015.12.002","article-title":"TNF and ROS crosstalk in inflammation","volume":"26","author":"Blaser","year":"2016","journal-title":"Trends Cell Biol"},{"key":"B157","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1831","article-title":"Thioredoxin-interacting protein links oxidative stress to inflammasome activation","volume":"11","author":"Zhou","year":"2010","journal-title":"Nat Immunol"},{"key":"B158","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/5601593","article-title":"ROS: crucial intermediators in the pathogenesis of intervertebral disc degeneration","volume":"2017","author":"Feng","year":"2017","journal-title":"Oxid Med Cell Longev"},{"key":"B159","doi-asserted-by":"publisher","DOI":"10.1002\/jor.24828","article-title":"Drp1-mediated mitochondrial fission is involved in oxidized low-density lipoprotein-induced AF cella poptosis","volume":"39","author":"Wu","year":"2021","journal-title":"J Orthop Res"},{"key":"B160","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/3765173","article-title":"High glucose-induced oxidative stress mediates apoptosis and extracellular matrix metabolic imbalances possibly via p38 MAPK activation in rat nucleus pulposus cells","volume":"2016","author":"Cheng","year":"2016","journal-title":"J Diabetes Res"},{"key":"B161","doi-asserted-by":"publisher","DOI":"10.1002\/jor.22361","article-title":"Mitochondrial bioenergetics, mass, and morphology are altered in cells of the degenerating human annulus","volume":"31","author":"Gruber","year":"2013","journal-title":"J Orthop Res"},{"key":"B162","doi-asserted-by":"publisher","DOI":"10.3109\/10715762.2010.498477","article-title":"Chemistry and biochemistry of lipid peroxidation products","volume":"44","author":"Gueraud","year":"2010","journal-title":"Free Radic Res"},{"key":"B163","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2011.03.065","article-title":"Thermosensitive chitosan-gelatin-glycerol phosphate hydrogel as a controlled release system of ferulic acid for nucleus pulposus regeneration","volume":"32","author":"Cheng","year":"2011","journal-title":"Biomaterials"},{"key":"B164","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202207216","article-title":"Polydopamine nanoparticles targeting ferroptosis mitigate intervertebral disc degeneration via reactive oxygen species depletion, iron ions chelation, and GPX4 ubiquitination suppression","volume":"10","author":"Yang","year":"2023","journal-title":"Adv Sci (Weinh)"},{"key":"B165","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2018.09.043","article-title":"The development of the concept of ferroptosis","volume":"133","author":"Hirschhorn","year":"2019","journal-title":"Free Radic Biol Med"},{"key":"B166","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2017.02.005","article-title":"Ferroptosis inhibition: mechanisms and opportunities","volume":"38","author":"Angeli","year":"2017","journal-title":"Trends Pharmacol Sci"},{"key":"B167","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-020-00324-8","article-title":"Ferroptosis: mechanisms, biology and role in disease","volume":"22","author":"Jiang","year":"2021","journal-title":"Nat Rev Mol Cell Biol"},{"key":"B168","doi-asserted-by":"publisher","DOI":"10.1016\/j.spinee.2025.10.009","article-title":"The STAT3\/S100A6\/P53\/SLC7A11 axis mediates intervertebral disc degeneration by regulating ferroptosis in nucleus pulposus cells and the metabolism of the extracellular matrix","volume":"26","author":"Yang","year":"2026","journal-title":"Spine J"},{"key":"B169","doi-asserted-by":"publisher","first-page":"3984","DOI":"10.1038\/s41598-025-87639-8","article-title":"PDE4B promotes ferroptosis in nucleus pulposus cells and is involved in intervertebral disc degeneration","volume":"15","author":"Xu","year":"2025","journal-title":"Sci Rep"},{"key":"B170","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2025.114455","article-title":"Oxidized low-density lipoprotein induced ferroptosis in nucleus pulposus cell contributes to intervertebral disc degeneration via LOX-1\/NF-\u03baB\/NOX signal","volume":"153","author":"Liu","year":"2025","journal-title":"Int Immunopharmacol"},{"key":"B171","doi-asserted-by":"publisher","DOI":"10.1002\/jgm.3488","article-title":"BACH1 promotes intervertebral disc degeneration by regulating HMOX1\/GPX4 to mediate oxidative stress, ferroptosis, and lipid metabolism in nucleus pulposus cells","volume":"25","author":"Yao","year":"2023","journal-title":"J Gene Med"},{"key":"B172","doi-asserted-by":"publisher","DOI":"10.1097\/js9.0000000000004980","article-title":"Melatonin attenuates oxidative stress-induced ferroptosis of nucleus pulposus cells and intervertebral disc degeneration via PI3K\/AKT-mTOR pathway","author":"Deng","year":"2026","journal-title":"Int J Surg"},{"key":"B173","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1007\/s00018-015-2052-6","article-title":"The endoplasmic reticulum: structure, function and response to cellular signaling","volume":"73","author":"Schwarz","year":"2016","journal-title":"Cell Mol Life Sci"},{"key":"B174","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathol-012513-104649","article-title":"The role of endoplasmic reticulum stress in human pathology","volume":"10","author":"Oakes","year":"2015","journal-title":"Annu Rev Pathol"},{"key":"B175","doi-asserted-by":"publisher","DOI":"10.1111\/febs.14972","article-title":"Impaired calcium homeostasis via advanced glycation end products promotes apoptosis through endoplasmic reticulum stress in human nucleus pulposus cells and exacerbates intervertebral disc degeneration in rats","volume":"286","author":"Luo","year":"2019","journal-title":"FEBS J"},{"key":"B176","doi-asserted-by":"publisher","DOI":"10.1111\/febs.13598","article-title":"Cell death induced by endoplasmic reticulum stress","volume":"283","author":"Iurlaro","year":"2016","journal-title":"FEBS J"},{"key":"B177","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2013.06.028","article-title":"ER stress-induced cell death mechanisms","volume":"1833","author":"Sano","year":"2013","journal-title":"Biochim Biophys Acta"},{"key":"B178","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202511781","article-title":"PACS-2 mitigates NPSC apoptosis and intervertebral disc degeneration by preserving MAM integrity via the SP1\/LRRK2\/Mfn2 axis","volume":"13","author":"Kang","year":"2026","journal-title":"Adv Sci (Weinh)"},{"key":"B179","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2023.1095307","article-title":"Sal003 alleviated intervertebral disc degeneration by inhibiting apoptosis and extracellular matrix degradation through suppressing endoplasmic reticulum stress pathway in rats","volume":"14","author":"Chen","year":"2023","journal-title":"Front Pharmacol"},{"key":"B180","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/8810698","article-title":"Reactive oxygen species regulate endoplasmic reticulum stress and ER-mitochondrial Ca(2+) crosstalk to promote programmed necrosis of rat nucleus pulposus cells under compression","volume":"2021","author":"Lin","year":"2021","journal-title":"Oxid Med Cell Longev"},{"key":"B181","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01706","article-title":"p38 MAPK facilitates crosstalk between endoplasmic reticulum stress and IL-6 release in the intervertebral disc","volume":"9","author":"Krupkova","year":"2018","journal-title":"Front Immunol"},{"key":"B182","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1038\/s42003-024-06248-9","article-title":"Palmitic acid induces lipid droplet accumulation and senescence in nucleus pulposus cells via ER-stress pathway","volume":"7","author":"Chen","year":"2024","journal-title":"Commun Biol"},{"key":"B183","doi-asserted-by":"publisher","DOI":"10.3390\/cells15020139","article-title":"Cytosolic immunostimulatory DNA ligands and DNA damage activate the integrated stress response, stress granule formation, and cytokine production","volume":"15","author":"Devale","year":"2026","journal-title":"Cells"},{"key":"B184","doi-asserted-by":"publisher","DOI":"10.1021\/acschemneuro.5c00792","article-title":"CHCHD2, rather than FBXO7, plays an essential role in modulating the MPP(+)-induced mtUPR","volume":"17","author":"Wen","year":"2026","journal-title":"ACS Chem Neurosci"},{"key":"B185","doi-asserted-by":"publisher","DOI":"10.1093\/toxres\/tfaf188","article-title":"Polygonum barbatum extract induces ER stress-mediated UPR and autophagy to suppress colorectal cancer growth","volume":"15","author":"Chang","year":"2026","journal-title":"Toxicol Res (Camb)"},{"key":"B186","doi-asserted-by":"publisher","first-page":"105168","DOI":"10.1016\/j.critrevonc.2026.105168","article-title":"ROS-mediated therapeutic approach through oxidative stress and cell signalling modulation","volume":"220","author":"Sahu","year":"2026","journal-title":"Crit Rev Oncol Hematol"},{"key":"B187","doi-asserted-by":"publisher","first-page":"111193","DOI":"10.1016\/j.cbpb.2026.111193","article-title":"Effects of phosphatidylserine supplementation on growth performance, lipid metabolism, antioxidant capacity, and inflammatory response of juvenile large yellow croaker (Larimichthys crocea) fed with high soybean oil diets","volume":"284","author":"Chen","year":"2026","journal-title":"Comp Biochem Physiol B Biochem Mol Biol"},{"key":"B188","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2025.1681230","article-title":"Effects of probiotics on lipid metabolism, oxidation, and inflammation in coronary heart disease: a systematic review and meta-analysis","volume":"12","author":"Yang","year":"2025","journal-title":"Front Nutr"},{"key":"B189","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2025.1753393","article-title":"Synergistic therapeutic strategies for metabolic dysfunction-associated steatohepatitis and type 2 diabetes mellitus: molecular insights and clinical advances","volume":"16","author":"Zhu","year":"2025","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B190","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2023.02.004","article-title":"Evaluation of PXL065 - deuterium-stabilized (R)-pioglitazone in patients with NASH: a phase II randomized placebo-controlled trial (DESTINY-1)","volume":"78","author":"Harrison","year":"2023","journal-title":"J Hepatol"},{"key":"B191","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(25)00979-1","article-title":"Antisense oligonucleotide DGAT-2 inhibitor, ION224, for metabolic dysfunction-associated steatohepatitis (ION224-CS2): results of a 51-week, multicentre, randomised, double-blind, placebo-controlled, phase 2 trial","volume":"406","author":"Loomba","year":"2025","journal-title":"Lancet"},{"key":"B192","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/j.jot.2025.05.010","article-title":"Activation of LAMP1-mediated lipophagy by sulforaphane inhibits cellular senescence and intervertebral disc degeneration","volume":"53","author":"Qin","year":"2025","journal-title":"J Orthop Translat"},{"key":"B193","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2025.119752","article-title":"Guiqi Huoxue capsule alleviates cervical spondylosis in rats: insights from 16S rRNA sequencing, lipidomics, and network pharmacology","volume":"347","author":"Tang","year":"2025","journal-title":"J Ethnopharmacol"},{"key":"B194","doi-asserted-by":"publisher","DOI":"10.1093\/ehjqcco\/qcag021","article-title":"Sustainable and effective lipid-lowering management: prevention strategies from the BRING-UP prevention study","author":"Colivicchi","year":"2026","journal-title":"Eur Heart J Qual Care Clin Outcomes"},{"key":"B195","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.s244","article-title":"Statins: low risk of side effects should prompt product label changes, researchers say","volume":"392","author":"Wise","year":"2026","journal-title":"Bmj"},{"key":"B196","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1186\/s12944-024-02311-w","article-title":"Association between lipid-lowering agents with intervertebral disc degeneration, sciatica and low back pain: a drug-targeted mendelian randomized study and cross-sectional observation","volume":"23","author":"Liu","year":"2024","journal-title":"Lipids Health Dis"},{"key":"B197","doi-asserted-by":"publisher","DOI":"10.2147\/jir.s461348","article-title":"Rosuvastatin: a potential therapeutic agent for inhibition of mechanical pressure-induced intervertebral disc degeneration","volume":"17","author":"Zhang","year":"2024","journal-title":"J Inflammation Res"},{"key":"B198","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1186\/s13018-025-05487-8","article-title":"The protective effect and experimental research progress of pleotropic statins in intervertebral disc degeneration","volume":"20","author":"Zhang","year":"2025","journal-title":"J Orthop Surg Res"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1843872\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T04:52:46Z","timestamp":1779339166000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1843872\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,21]]},"references-count":198,"alternative-id":["10.3389\/fimmu.2026.1843872"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1843872","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,21]]},"article-number":"1843872"}}