{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T01:34:05Z","timestamp":1793842445915,"version":"4.6.1"},"reference-count":64,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82172381"],"award-info":[{"award-number":["82172381"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82302760"],"award-info":[{"award-number":["82302760"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82472493"],"award-info":[{"award-number":["82472493"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Proliferation"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Intervertebral disc degeneration (IVDD) is a major contributor to low back pain, but the immune\u2010metabolic events that sustain disc inflammation remain poorly defined. Here, we investigated whether disturbed macrophage lipid handling promotes IVDD by coupling cellular senescence to defective efferocytosis. Clinical magnetic resonance imaging and biochemical profiling showed that advanced IVDD was accompanied by increased disc fat fraction and systemic lipid abnormalities. Mendelian randomisation, bulk transcriptomics, machine\u2010learning modelling and single\u2010cell RNA sequencing further linked lipid metabolic disturbance to immune remodelling in degenerative discs, and identified TIAM2, SLC44A4, PPT1 and PTGDS as lipid metabolism\u2010related hub genes associated with IVDD. At the single\u2010cell level, disc macrophages with low glycerophospholipid metabolism scores showed higher senescence activity, a more inflammatory polarisation state and reduced efferocytosis\u2010related signatures. Functional studies in bone marrow\u2010derived macrophages indicated that lipid overload promoted lipid droplet accumulation, lipid peroxidation, impaired lipophagy and cholesterol efflux, activation of the p53\/p21 senescence pathway, and reduced apoptotic nucleus pulposus cell clearance. Restoring lipid homeostasis with rosuvastatin enhanced lipophagy, recovered ABCA1\/ABCG1\u2010mediated cholesterol export, attenuated macrophage senescence and inflammatory activation and improved efferocytosis. In a rat needle puncture model, local rosuvastatin delivery alleviated disc structural damage, preserved proteoglycan content, balanced extracellular matrix metabolism and reduced macrophage senescence and inflammatory markers. In conclusion, this study supports macrophage lipid homeostasis as an important regulator of IVDD\u2010associated immune dysfunction through senescence\u2010associated impairment of efferocytosis.<\/jats:p>","DOI":"10.1111\/cpr.70271","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T05:29:30Z","timestamp":1787203770000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Macrophage Lipid Homeostasis Drives\n                    <scp>IVDD<\/scp>\n                    via a Senescence\u2010Dependent Impairment of Efferocytosis"],"prefix":"10.1111","author":[{"given":"Jinyu","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Orthopedic Surgery Changzheng Hospital, Naval Medical University  Shanghai P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-3453-3671","authenticated-orcid":false,"given":"Shiyong","family":"Ling","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics Shanghai Jing'an District Zhabei Central Hospital  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9737-0224","authenticated-orcid":false,"given":"Qi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Changzheng Hospital, Naval Medical University  Shanghai P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuege","family":"Qiao","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Naval Medical University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianpeng","family":"Xing","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Changzheng Hospital, Naval Medical University  Shanghai P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyang","family":"Ji","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Changzheng Hospital, Naval Medical University  Shanghai P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-5836-8886","authenticated-orcid":false,"given":"Linhui","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Changzheng Hospital, Naval Medical University  Shanghai P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9062-4735","authenticated-orcid":false,"given":"Chen","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Changzheng Hospital, Naval Medical University  Shanghai P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhishen","family":"Niu","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Changzheng Hospital, Naval Medical University  Shanghai P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9069-9481","authenticated-orcid":false,"given":"Lei","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Health Management, Faculty of Military Health Service Naval Medical University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baolian","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Radiology Changzheng Hospital, Naval Medical University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0272-8383","authenticated-orcid":false,"given":"Kaiqiang","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Changzheng Hospital, Naval Medical University  Shanghai P. R. China"},{"name":"Department of Orthopedics Naval Medical Center of PLA  Shanghai P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2133-0108","authenticated-orcid":false,"given":"Jiangang","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Changzheng Hospital, Naval Medical University  Shanghai P. R. 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