{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T00:45:54Z","timestamp":1792889154051,"version":"4.5.0"},"reference-count":125,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T00:00:00Z","timestamp":1747180800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["JOR Spine"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Intervertebral disc degeneration (IVDD) is a leading cause of low back pain (LBP), contributing significantly to global disability and productivity loss. Its pathogenesis involves complex processes, including inflammation, cellular senescence, angiogenesis, fibrosis, neural ingrowth, and sensitization. Emerging evidence highlights macrophages as central immune regulators infiltrating degenerated discs, with macrophage polarization implicated in IVDD progression. However, the mechanisms linking macrophage polarization to IVDD pathology remain poorly elucidated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A comprehensive literature review was conducted by searching major databases (PubMed, Web of Science, and Scopus) for studies published in the last decade (2014\u20132024). Keywords included \u201cintervertebral disc degeneration,\u201d \u201cmacrophage polarization,\u201d \u201cinflammation,\u201d \u201csenescence,\u201d and \u201ctherapeutic strategies.\u201d Relevant articles were selected, analyzed, and synthesized to evaluate the role of macrophage polarization in IVDD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Macrophage polarization dynamically influences IVDD through multiple pathways. Pro\u2010inflammatory M1 macrophages exacerbate disc degeneration by amplifying inflammatory cytokines (e.g., TNF\u2010\u03b1, IL\u20101\u03b2), promoting cellular senescence, and stimulating abnormal angiogenesis and neural ingrowth. In contrast, anti\u2010inflammatory M2 macrophages may mitigate degeneration by suppressing inflammation and enhancing tissue repair. Therapeutic strategies targeting macrophage polarization include pharmacological agents (e.g., cytokines, small\u2010molecule inhibitors), biologic therapies, gene editing, and physical interventions. Challenges persist, such as incomplete understanding of polarization triggers, lack of targeted delivery systems, and limited translational success in preclinical models.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Macrophage polarization is a pivotal regulator of IVDD pathology, offering promising therapeutic targets. Future research should focus on elucidating polarization mechanisms, optimizing spatiotemporal control of macrophage phenotypes, and developing personalized therapies. Addressing these challenges may advance innovative strategies to halt or reverse IVDD progression, ultimately improving clinical outcomes for LBP patients.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jsp2.70065","type":"journal-article","created":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T17:04:07Z","timestamp":1747242247000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Mechanisms and Therapeutic Strategies of Macrophage Polarization in Intervertebral Disc Degeneration"],"prefix":"10.1002","volume":"8","author":[{"given":"Kaiyuan","family":"Zheng","sequence":"first","affiliation":[{"name":"Department of Rehabilitation Medicine, Intensive Care Medicine Affiliated Hospital of North Sichuan Medical College  Nanchong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine, Intensive Care Medicine Affiliated Hospital of North Sichuan Medical College  Nanchong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory The First People's Hospital of Guangyuan  Guangyuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaomin","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine, Intensive Care Medicine Affiliated Hospital of North Sichuan Medical College  Nanchong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine, Intensive Care Medicine Affiliated Hospital of North Sichuan Medical College  Nanchong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9881-7699","authenticated-orcid":false,"given":"Lianlin","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine Suining Central Hospital  Suining China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinxu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine, Intensive Care Medicine Affiliated Hospital of North Sichuan Medical College  Nanchong China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,5,14]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2665-9913(23)00098-X"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2023.06.010"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.34347"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41434-018-0004-0"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2013.160"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21062135"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2013.11.004"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1080\/03008207.2023.2212051"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvg.20417"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18071545"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.02.028"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12034"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2020.173090"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00011-015-0874-1"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12026-012-8291-9"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1100\/2011\/213962"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/816460"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/imm.12910"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/JLB.3RU1018-378RR"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24087493"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2010.52"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4338"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-022516-034339"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1003153"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom13040686"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11916-023-01188-1"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23126612"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.922173"},{"key":"e_1_2_13_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2023.110844"},{"key":"e_1_2_13_31_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12951-024-02556-8"},{"key":"e_1_2_13_32_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.701087"},{"key":"e_1_2_13_33_1","doi-asserted-by":"publisher","DOI":"10.1097\/BRS.0000000000002953"},{"key":"e_1_2_13_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2019.01.004"},{"key":"e_1_2_13_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2019.106004"},{"key":"e_1_2_13_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10753-019-00965-8"},{"key":"e_1_2_13_37_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.796974"},{"key":"e_1_2_13_38_1","doi-asserted-by":"publisher","DOI":"10.3389\/fvets.2020.00032"},{"key":"e_1_2_13_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-024-01168-4"},{"key":"e_1_2_13_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2005.12.002"},{"key":"e_1_2_13_41_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.204729"},{"key":"e_1_2_13_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2023.e19951"},{"key":"e_1_2_13_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00586-019-06220-w"},{"key":"e_1_2_13_44_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.102909"},{"key":"e_1_2_13_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2019.03.020"},{"key":"e_1_2_13_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2019.10.002"},{"key":"e_1_2_13_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.25292"},{"key":"e_1_2_13_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/btm2.10500"},{"key":"e_1_2_13_49_1","doi-asserted-by":"publisher","DOI":"10.34133\/bmr.0047"},{"key":"e_1_2_13_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2023.09.010"},{"key":"e_1_2_13_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-023-01502-8"},{"key":"e_1_2_13_52_1","doi-asserted-by":"publisher","DOI":"10.1042\/CS20190893"},{"key":"e_1_2_13_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/npjamd.2016.18"},{"key":"e_1_2_13_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2024.01.001"},{"key":"e_1_2_13_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43587-024-00694-0"},{"key":"e_1_2_13_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2023.112424"},{"key":"e_1_2_13_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41413-023-00309-1"},{"key":"e_1_2_13_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2020.106294"},{"key":"e_1_2_13_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2014.02.014"},{"key":"e_1_2_13_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2024.101943"},{"key":"e_1_2_13_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2023.111262"},{"key":"e_1_2_13_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2006.08.261"},{"key":"e_1_2_13_63_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.brs.0000162624.95262.73"},{"key":"e_1_2_13_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2020.118778"},{"issue":"8","key":"e_1_2_13_65_1","article-title":"Immunomorphogenesis in Degenerative Disc Disease: The Role of Proinflammatory Cytokines and Angiogenesis Factors","volume":"11","author":"Pravdyuk N. G.","year":"2023","journal-title":"Biomedicine"},{"key":"e_1_2_13_66_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00586-013-2842-1"},{"key":"e_1_2_13_67_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvq049"},{"key":"e_1_2_13_68_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2017.11"},{"key":"e_1_2_13_69_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10555-021-09958-2"},{"key":"e_1_2_13_70_1","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/9624760"},{"key":"e_1_2_13_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2021.06.010"},{"key":"e_1_2_13_72_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41413-021-00163-z"},{"key":"e_1_2_13_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2013.12.008"},{"key":"e_1_2_13_74_1","doi-asserted-by":"publisher","DOI":"10.1093\/neuros\/nyx149"},{"key":"e_1_2_13_75_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.21210"},{"key":"e_1_2_13_76_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.20727"},{"key":"e_1_2_13_77_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2023.03.014"},{"key":"e_1_2_13_78_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41413-022-00211-2"},{"key":"e_1_2_13_79_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-021-02690-w"},{"key":"e_1_2_13_80_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2016.02.015"},{"key":"e_1_2_13_81_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2019020111"},{"key":"e_1_2_13_82_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells10020436"},{"key":"e_1_2_13_83_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2016.48"},{"issue":"23","key":"e_1_2_13_84_1","first-page":"12025","article-title":"TGF\u2010\u03b21 Aggravates Degenerative Nucleus Pulposus Cells Inflammation and Fibrosis Through the Upregulation of Angiopoietin\u2010Like Protein 2 Expression","volume":"24","author":"Cui L.","year":"2020","journal-title":"European Review for Medical and Pharmacological Sciences"},{"key":"e_1_2_13_85_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.10.077"},{"key":"e_1_2_13_86_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.760138"},{"key":"e_1_2_13_87_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1875-5364(23)60444-3"},{"key":"e_1_2_13_88_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.10585"},{"key":"e_1_2_13_89_1","doi-asserted-by":"publisher","DOI":"10.1111\/joa.12817"},{"key":"e_1_2_13_90_1","doi-asserted-by":"publisher","DOI":"10.1097\/BRS.0b013e318263ba59"},{"key":"e_1_2_13_91_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075\u2010015\u20100889\u20106"},{"key":"e_1_2_13_92_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bja.2019.06.024"},{"key":"e_1_2_13_93_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-014-0416-1"},{"key":"e_1_2_13_94_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.23888"},{"key":"e_1_2_13_95_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-39657-6"},{"key":"e_1_2_13_96_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2021.04.007"},{"key":"e_1_2_13_97_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2021.12.005"},{"key":"e_1_2_13_98_1","doi-asserted-by":"publisher","DOI":"10.2174\/1871530322666221006114557"},{"key":"e_1_2_13_99_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI164472"},{"key":"e_1_2_13_100_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-014-8790-x"},{"key":"e_1_2_13_101_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-13-0080"},{"key":"e_1_2_13_102_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2023.02.018"},{"key":"e_1_2_13_103_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046\u2010018\u20100878\u20100"},{"key":"e_1_2_13_104_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13018\u2010022\u201003438\u20101"},{"key":"e_1_2_13_105_1","doi-asserted-by":"publisher","DOI":"10.1159\/000430126"},{"key":"e_1_2_13_106_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2017.7464"},{"key":"e_1_2_13_107_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2023.1156821"},{"key":"e_1_2_13_108_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2020.00700"},{"key":"e_1_2_13_109_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00337312"},{"key":"e_1_2_13_110_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioactmat.2024.02.021"},{"key":"e_1_2_13_111_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2022.108962"},{"key":"e_1_2_13_112_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2022.113408"},{"key":"e_1_2_13_113_1","doi-asserted-by":"publisher","DOI":"10.1177\/20417314211021679"},{"key":"e_1_2_13_114_1","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.201901186"},{"key":"e_1_2_13_115_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2023.08.023"},{"key":"e_1_2_13_116_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.3c08097"},{"key":"e_1_2_13_117_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24010390"},{"key":"e_1_2_13_118_1","doi-asserted-by":"publisher","DOI":"10.1113\/jp285871"},{"key":"e_1_2_13_119_1","doi-asserted-by":"publisher","DOI":"10.1002\/jsp2.70036"},{"key":"e_1_2_13_120_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2025.114131"},{"key":"e_1_2_13_121_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00614"},{"key":"e_1_2_13_122_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms232214180"},{"key":"e_1_2_13_123_1","doi-asserted-by":"publisher","DOI":"10.1177\/1947601911423031"},{"key":"e_1_2_13_124_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010018\u201030185\u20103"},{"key":"e_1_2_13_125_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2024.1516609"},{"key":"e_1_2_13_126_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioactmat.2023.07.003"}],"container-title":["JOR SPINE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jsp2.70065","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,26]],"date-time":"2025-06-26T15:37:40Z","timestamp":1750952260000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jsp2.70065"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,14]]},"references-count":125,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,6]]}},"alternative-id":["10.1002\/jsp2.70065"],"URL":"https:\/\/doi.org\/10.1002\/jsp2.70065","archive":["Portico"],"relation":{},"ISSN":["2572-1143","2572-1143"],"issn-type":[{"value":"2572-1143","type":"print"},{"value":"2572-1143","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,14]]},"assertion":[{"value":"2025-01-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-26","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70065"}}