{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T17:19:59Z","timestamp":1783185599076,"version":"3.54.6"},"reference-count":65,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2022,7,6]],"date-time":"2022-07-06T00:00:00Z","timestamp":1657065600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001702","name":"AO Foundation","doi-asserted-by":"publisher","award":["NeoDisc"],"award-info":[{"award-number":["NeoDisc"]}],"id":[{"id":"10.13039\/501100001702","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002732","name":"AOSpine","doi-asserted-by":"publisher","award":["Theranostic"],"award-info":[{"award-number":["Theranostic"]}],"id":[{"id":"10.13039\/501100002732","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["JOR Spine"],"published-print":{"date-parts":[[2022,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>During the intervertebral disc (IVD) degeneration process, initial degenerative events occur at the extracellular matrix level, with the appearance of neoepitope peptides formed by the cleavage of aggrecan and collagen. This study aims to elucidate the spatial and temporal alterations of aggrecan and collagen neoepitope level during IVD degeneration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Bovine caudal IVDs were cultured under four different conditions to mimic different degenerative situations. Samples cultured after 1\u2010 or 8\u2010days were collected for analysis. Human IVD samples were obtained from patients diagnosed with lumbar disc herniation (LDH) or adolescent idiopathic scoliosis (AIS). After immunohistochemical (IHC) staining of Aggrecanase Cleaved C\u2010terminus Aggrecan Neoepitope (NB100), MMP Cleaved C\u2010terminus Aggrecan Neoepitope (MMPCC), Collagen Type 1\u03b11 1\/4 fragment (C1\u03b11) and Collagenase Cleaved Type I and II Collagen Neoepitope (C1,2C), staining optical density (OD)\/area in extracellular matrix (OECM) and pericellular zone (OPCZ) were analyzed. Conditioned media of the bovine IVD was collected to measure protein level of inflammatory cytokines and C1,2C.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>For the bovine IVD sections, the aggrecan MMPCC neoepitope was accumulated in nucleus pulposus (NP) and cartilage endplate (EP) regions following mechanical overload in the one strike model after long\u2010term culture; as for the TNF\u2010\u03b1 induced degeneration, the OECM and OPCZ of collagen C1,2C neoepitope was significantly increased in the outer AF region after long\u2010term culture; moreover, the C1,2C was only detected in conditioned medium from TNF\u2010\u03b1 injection + Degenerative loading group after 8\u2009days of culture. LDH patients showed higher MMPCC OECM in NP and higher C1,2C OECM in AF region compared with AIS patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In summary, aggrecan and collagen neoepitope profiles showed degeneration induction trigger\u2010 and region\u2010specific differences in the IVD organ culture models. Different IVD degeneration types are correlated with specific neoepitope expression profiles. These neoepitopes may be helpful as biomarkers of ECM degradation in early IVD degeneration and indicators of different degeneration phenotypes.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jsp2.1215","type":"journal-article","created":{"date-parts":[[2022,7,7]],"date-time":"2022-07-07T06:40:24Z","timestamp":1657176024000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Neoepitope fragments as biomarkers for different phenotypes of intervertebral disc degeneration"],"prefix":"10.1002","volume":"5","author":[{"given":"Shangbin","family":"Cui","sequence":"first","affiliation":[{"name":"AO Research Institute Davos  Davos Switzerland"},{"name":"Guangdong Provincial Key Laboratory of Orthopedics and Traumatology The First Affiliated Hospital of Sun Yat\u2010Sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenyue","family":"Li","sequence":"additional","affiliation":[{"name":"AO Research Institute Davos  Davos Switzerland"},{"name":"Zhejiang University\u2010University of Edinburgh Institute (ZJU\u2010UoE Institute) Zhejiang University  Haining China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graciosa Q.","family":"Teixeira","sequence":"additional","affiliation":[{"name":"Institute of Orthopedic Research and Biomechanics, Centre for Trauma Research Ulm (ZTF Ulm) Ulm University  Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelia","family":"Neidlinger\u2010Wilke","sequence":"additional","affiliation":[{"name":"Institute of Orthopedic Research and Biomechanics, Centre for Trauma Research Ulm (ZTF Ulm) Ulm University  Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans\u2010Joachim","family":"Wilke","sequence":"additional","affiliation":[{"name":"Institute of Orthopedic Research and Biomechanics, Centre for Trauma Research Ulm (ZTF Ulm) Ulm University  Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1288-2149","authenticated-orcid":false,"given":"Lisbet","family":"Haglund","sequence":"additional","affiliation":[{"name":"Department of Surgery and Shriners Hospital for Children McGill University  Montreal Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongwei","family":"Ouyang","sequence":"additional","affiliation":[{"name":"Zhejiang University\u2010University of Edinburgh Institute (ZJU\u2010UoE Institute) Zhejiang University  Haining China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. Geoff","family":"Richards","sequence":"additional","affiliation":[{"name":"AO Research Institute Davos  Davos Switzerland"},{"name":"Guangdong Provincial Key Laboratory of Orthopedics and Traumatology The First Affiliated Hospital of Sun Yat\u2010Sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9552-3653","authenticated-orcid":false,"given":"Sibylle","family":"Grad","sequence":"additional","affiliation":[{"name":"AO Research Institute Davos  Davos Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0262-1412","authenticated-orcid":false,"given":"Mauro","family":"Alini","sequence":"additional","affiliation":[{"name":"AO Research Institute Davos  Davos 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