{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T06:10:32Z","timestamp":1788502232249,"version":"build-2803163510"},"reference-count":41,"publisher":"Elsevier BV","issue":"1","license":[{"start":{"date-parts":[[2024,1,1]],"date-time":"2024-01-01T00:00:00Z","timestamp":1704067200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2024,1,1]],"date-time":"2024-01-01T00:00:00Z","timestamp":1704067200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"vor","delay-in-days":366,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81802130"],"award-info":[{"award-number":["81802130"]}],"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":["81960407"],"award-info":[{"award-number":["81960407"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2018M630968"],"award-info":[{"award-number":["2018M630968"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2018A030310462"],"award-info":[{"award-number":["2018A030310462"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003785","name":"Guangdong Medical Research Foundation","doi-asserted-by":"publisher","award":["B2023375"],"award-info":[{"award-number":["B2023375"]}],"id":[{"id":"10.13039\/501100003785","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004479","name":"Natural Science Foundation of Jiangxi Province","doi-asserted-by":"publisher","award":["20192BAB205029"],"award-info":[{"award-number":["20192BAB205029"]}],"id":[{"id":"10.13039\/501100004479","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","oarsijournal.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Osteoarthritis and Cartilage"],"published-print":{"date-parts":[[2024,1]]},"DOI":"10.1016\/j.joca.2023.09.010","type":"journal-article","created":{"date-parts":[[2023,10,4]],"date-time":"2023-10-04T21:04:43Z","timestamp":1696453483000},"page":"66-81","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":21,"title":["CD206+ M2-like macrophages protect against intervertebral disc degeneration partially by targeting R-spondin-2"],"prefix":"10.1016","volume":"32","author":[{"given":"Xiao-Chuan","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong-Long","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiong-Hui","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen-Wu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shao-Jian","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong-Chun","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping-Fan","family":"Mo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Liang","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiang-You","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun-Ming","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao-Hong","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.joca.2023.09.010_bib1","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/S0140-6736(21)00733-9","article-title":"Low back pain","volume":"398","author":"Knezevic","year":"2021","journal-title":"The Lancet"},{"key":"10.1016\/j.joca.2023.09.010_bib2","doi-asserted-by":"crossref","first-page":"581","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":"The Lancet"},{"key":"10.1016\/j.joca.2023.09.010_bib3","doi-asserted-by":"crossref","DOI":"10.3389\/fsurg.2022.814531","article-title":"Emerging issues questioning the current treatment strategies for lumbar disc herniation","volume":"9","author":"Wan","year":"2022","journal-title":"Front Surg"},{"key":"10.1016\/j.joca.2023.09.010_bib4","doi-asserted-by":"crossref","first-page":"1703","DOI":"10.1002\/jor.24590","article-title":"Investigation of resident and recruited macrophages following disc injury in mice","volume":"38","author":"Kawakubo","year":"2020","journal-title":"J Orthop Res"},{"key":"10.1016\/j.joca.2023.09.010_bib5","article-title":"Revealing the immune infiltration landscape and identifying diagnostic biomarkers for lumbar disc herniation","volume":"12","author":"Wang","year":"2021","journal-title":"Front Immunol"},{"key":"10.1016\/j.joca.2023.09.010_bib6","doi-asserted-by":"crossref","first-page":"1238","DOI":"10.1002\/jor.24560","article-title":"Long-term histological analysis of innervation and macrophage infiltration in a mouse model of intervertebral disc injury-induced low back pain","volume":"38","author":"Lee","year":"2019","journal-title":"J Orthop Res"},{"key":"10.1016\/j.joca.2023.09.010_bib7","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/j.spinee.2017.09.018","article-title":"Accumulation and localization of macrophage phenotypes with human intervertebral disc degeneration","volume":"18","author":"Nakazawa","year":"2017","journal-title":"Spine J"},{"key":"10.1016\/j.joca.2023.09.010_bib8","doi-asserted-by":"crossref","first-page":"E520","DOI":"10.1097\/BRS.0000000000002953","article-title":"Secreted factors from intervertebral disc cells and infiltrating macrophages promote degenerated intervertebral disc catabolism","volume":"44","author":"Yang","year":"2018","journal-title":"Spine"},{"key":"10.1016\/j.joca.2023.09.010_bib9","article-title":"Influence of macrophage polarization in herniated nucleus pulposus tissue on clinical efficacy after lumbar discectomy","volume":"26","author":"Li","year":"2023","journal-title":"JOR Spine"},{"key":"10.1016\/j.joca.2023.09.010_bib10","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1016\/j.joca.2020.01.007","article-title":"Macrophages regulate the progression of osteoarthritis","volume":"28","author":"Zhang","year":"2020","journal-title":"Osteoarthr Cartil"},{"key":"10.1016\/j.joca.2023.09.010_bib11","doi-asserted-by":"crossref","first-page":"111","DOI":"10.3389\/fimmu.2020.00111","article-title":"Macrophage: a potential target on cartilage regeneration","volume":"11","author":"Fernandes","year":"2020","journal-title":"Front Immunol"},{"key":"10.1016\/j.joca.2023.09.010_bib12","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/j.immuni.2016.02.015","article-title":"Macrophages in tissue repair, regeneration, and fibrosis","volume":"44","author":"Wynn","year":"2016","journal-title":"Immunity"},{"key":"10.1016\/j.joca.2023.09.010_bib13","doi-asserted-by":"crossref","first-page":"5155","DOI":"10.1038\/srep05155","article-title":"Activation of Rheb, but not of mTORC1, impairs spine synapse morphogenesis in tuberous sclerosis complex","volume":"4","author":"Yasuda","year":"2014","journal-title":"Sci Rep"},{"key":"10.1016\/j.joca.2023.09.010_bib14","doi-asserted-by":"crossref","first-page":"2834","DOI":"10.1038\/ncomms3834","article-title":"The TSC-mTOR pathway regulates macrophage polarization","volume":"4","author":"Byles","year":"2013","journal-title":"Nat Commun"},{"key":"10.1016\/j.joca.2023.09.010_bib15","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1126\/science.1147379","article-title":"Rheb activates mTOR by antagonizing its endogenous inhibitor, FKBP38","volume":"318","author":"Bai","year":"2007","journal-title":"Science"},{"key":"10.1016\/j.joca.2023.09.010_bib16","doi-asserted-by":"crossref","first-page":"1829","DOI":"10.1002\/jbmr.3172","article-title":"mTORC1 inhibits NF-kappaB\/NFATc1 signaling and prevents osteoclast precursor differentiation, in vitro and in mice","volume":"32","author":"Zhang","year":"2017","journal-title":"J Bone Miner Res"},{"key":"10.1016\/j.joca.2023.09.010_bib17","doi-asserted-by":"crossref","first-page":"2488","DOI":"10.1002\/jor.25292","article-title":"M2 macrophage-conditioned medium inhibits intervertebral disc degeneration in a tumor necrosis factor-\u03b1-rich environment","volume":"40","author":"Li","year":"2022","journal-title":"J Orthop Res"},{"key":"10.1016\/j.joca.2023.09.010_bib18","doi-asserted-by":"crossref","first-page":"5051","DOI":"10.1038\/s41467-018-07360-1","article-title":"Preclinical development of a microRNA-based therapy for intervertebral disc degeneration","volume":"9","author":"Ji","year":"2018","journal-title":"Nat Commun"},{"key":"10.1016\/j.joca.2023.09.010_bib19","doi-asserted-by":"crossref","first-page":"1524","DOI":"10.1136\/annrheumdis-2018-213450","article-title":"Synovial macrophage M1 polarisation exacerbates experimental osteoarthritis partially through R-spondin-2","volume":"77","author":"Zhang","year":"2018","journal-title":"Ann Rheum Dis"},{"key":"10.1016\/j.joca.2023.09.010_bib20","doi-asserted-by":"crossref","first-page":"1508","DOI":"10.3389\/fimmu.2019.01508","article-title":"Macrophages down-regulate gene expression of intervertebral disc degenerative markers under a pro-inflammatory microenvironment","volume":"10","author":"Silva","year":"2019","journal-title":"Front Immunol"},{"key":"10.1016\/j.joca.2023.09.010_bib21","article-title":"Macrophage polarization regulates intervertebral disc degeneration by modulating cell proliferation, inflammation mediator secretion, and extracellular matrix metabolism","volume":"13","author":"Li","year":"2022","journal-title":"Front Immunol"},{"key":"10.1016\/j.joca.2023.09.010_bib22","doi-asserted-by":"crossref","first-page":"1798","DOI":"10.1002\/jor.24308","article-title":"Changes in nerve growth factor expression and macrophage phenotype following intervertebral disc injury in mice","volume":"37","author":"Nakawaki","year":"2019","journal-title":"J Orthop Res"},{"key":"10.1016\/j.joca.2023.09.010_bib23","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1097\/00007632-200004010-00017","article-title":"Influence of macrophage infiltration of herniated lumbar disc tissue on outcome after lumbar disc surgery","volume":"25","author":"Woertgen","year":"2000","journal-title":"Spine"},{"key":"10.1016\/j.joca.2023.09.010_bib24","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1007\/s007010050245","article-title":"Macrophage tissue infiltration, clinical symptoms, and signs in patients with lumbar disc herniation. A clinicopathological study on 179 patients","volume":"140","author":"Rothoerl","year":"1998","journal-title":"Acta Neurochir"},{"key":"10.1016\/j.joca.2023.09.010_bib25","doi-asserted-by":"crossref","first-page":"1649","DOI":"10.1007\/s00586-019-06220-w","article-title":"The contradictory effect of macrophage-related cytokine expression in lumbar disc herniations: a systematic review","volume":"29","author":"Djuric","year":"2020","journal-title":"Eur Spine J"},{"key":"10.1016\/j.joca.2023.09.010_bib26","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.spinee.2015.10.038","article-title":"Elevated levels of tumor necrosis factor-alpha and TNFR1 in recurrent herniated lumbar discs correlate with chronicity of postoperative sciatic pain","volume":"16","author":"Andrade","year":"2016","journal-title":"Spine J"},{"key":"10.1016\/j.joca.2023.09.010_bib27","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.bbi.2015.01.008","article-title":"Serum levels of the pro-inflammatory interleukins 6 (IL-6) and -8 (IL-8) in patients with lumbar radicular pain due to disc herniation: a 12-month prospective study","volume":"46","author":"Pedersen","year":"2015","journal-title":"Brain Behav Immun"},{"key":"10.1016\/j.joca.2023.09.010_bib28","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.1002\/jor.25480","article-title":"Investigation of macrophage polarization in herniated nucleus pulposus of patients with lumbar intervertebral disc herniation","volume":"41","author":"Li","year":"2022","journal-title":"J Orthop Res"},{"key":"10.1016\/j.joca.2023.09.010_bib29","article-title":"M2a macrophage-secreted CHI3L1 promotes extracellular matrix metabolic imbalances via activation of IL-13Ralpha2\/MAPK pathway in rat intervertebral disc degeneration","volume":"12","author":"Li","year":"2021","journal-title":"Front Immunol"},{"key":"10.1016\/j.joca.2023.09.010_bib30","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1038\/s41419-018-1246-x","article-title":"Transgenic mice overexpressing human TNF-alpha experience early onset spontaneous intervertebral disc herniation in the absence of overt degeneration","volume":"10","author":"Gorth","year":"2018","journal-title":"Cell Death Dis"},{"key":"10.1016\/j.joca.2023.09.010_bib31","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1016\/j.spinee.2021.12.005","article-title":"Polarization of infiltrating macrophages in the outer annulus fibrosus layer associated with the process of intervertebral disc degeneration and neural ingrowth in the human cervical spine","volume":"22","author":"Yamagishi","year":"2022","journal-title":"Spine J"},{"key":"10.1016\/j.joca.2023.09.010_bib32","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1016\/j.spinee.2021.10.014","article-title":"Heterogeneous macrophages contribute to the pathology of disc herniation induced radiculopathy","volume":"22","author":"Jin","year":"2022","journal-title":"Spine J"},{"key":"10.1016\/j.joca.2023.09.010_bib33","doi-asserted-by":"crossref","first-page":"685","DOI":"10.7150\/ijms.42238","article-title":"The immune privilege of the intervertebral disc: implications for intervertebral disc degeneration treatment","volume":"17","author":"Sun","year":"2020","journal-title":"Int J Med Sci"},{"key":"10.1016\/j.joca.2023.09.010_bib34","first-page":"1009","article-title":"Immune cascades in human intervertebral disc: the pros and cons","volume":"6","author":"Sun","year":"2013","journal-title":"Int J Clin Exp Pathol"},{"key":"10.1016\/j.joca.2023.09.010_bib35","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1016\/j.mehy.2013.06.014","article-title":"Molecular immunotherapy might shed a light on the treatment strategies for disc degeneration and herniation","volume":"81","author":"Sun","year":"2013","journal-title":"Med Hypotheses"},{"key":"10.1016\/j.joca.2023.09.010_bib36","doi-asserted-by":"crossref","first-page":"E149","DOI":"10.1097\/BRS.0000000000004222","article-title":"Distribution and polarization of hematogenous macrophages associated with the progression of intervertebral disc degeneration","volume":"47","author":"Yamamoto","year":"2022","journal-title":"Spine"},{"key":"10.1016\/j.joca.2023.09.010_bib37","doi-asserted-by":"crossref","DOI":"10.1111\/cpr.13338","article-title":"Emerging role and therapeutic implication of mTOR signalling in intervertebral disc degeneration","volume":"56","author":"Chen","year":"2023","journal-title":"Cell Prolif"},{"key":"10.1016\/j.joca.2023.09.010_bib38","doi-asserted-by":"crossref","DOI":"10.1002\/jsp2.1082","article-title":"Autophagy and mTOR signaling during intervertebral disc aging and degeneration","volume":"3","author":"Yurube","year":"2020","journal-title":"JOR Spine"},{"key":"10.1016\/j.joca.2023.09.010_bib39","doi-asserted-by":"crossref","first-page":"4696","DOI":"10.1038\/ncomms5696","article-title":"TSC1 controls macrophage polarization to prevent inflammatory disease","volume":"5","author":"Zhu","year":"2014","journal-title":"Nat Commun"},{"key":"10.1016\/j.joca.2023.09.010_bib40","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.matbio.2014.06.003","article-title":"R-spondins: novel matricellular regulators of the skeleton","volume":"37","author":"Knight","year":"2014","journal-title":"Matrix Biol"},{"key":"10.1016\/j.joca.2023.09.010_fur1","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1186\/s13075-019-1990-z","article-title":"JAG2\/Notch2 inhibits intervertebral disc degeneration by modulating cell proliferation, apoptosis, and extracellular matrix","volume":"21","author":"Long","year":"2019","journal-title":"Arthritis Res Ther"}],"container-title":["Osteoarthritis and Cartilage"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1063458423009433?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1063458423009433?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T04:01:37Z","timestamp":1761019297000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1063458423009433"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1]]},"references-count":41,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024,1]]}},"alternative-id":["S1063458423009433"],"URL":"https:\/\/doi.org\/10.1016\/j.joca.2023.09.010","relation":{},"ISSN":["1063-4584"],"issn-type":[{"value":"1063-4584","type":"print"}],"subject":[],"published":{"date-parts":[[2024,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"CD206+ M2-like macrophages protect against intervertebral disc degeneration partially by targeting R-spondin-2","name":"articletitle","label":"Article Title"},{"value":"Osteoarthritis and Cartilage","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.joca.2023.09.010","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2023 Osteoarthritis Research Society International. Published by Elsevier Ltd.","name":"copyright","label":"Copyright"}]}}