{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T15:36:07Z","timestamp":1784734567532,"version":"3.55.0"},"reference-count":46,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,2,10]],"date-time":"2025-02-10T00:00:00Z","timestamp":1739145600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010665","name":"H2020 Marie Sk\u0142odowska-Curie Actions","doi-asserted-by":"publisher","award":["#955735"],"award-info":[{"award-number":["#955735"]}],"id":[{"id":"10.13039\/100010665","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["JOR Spine"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>This study investigates the native presence and potential anabolic effects of interleukin (IL)\u20104 and IL\u201010 in the human intervertebral disc (IVD).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Human nucleus pulposus (NP) cells cultured in 3D from trauma and degenerate IVDs and NP explants were stimulated with 10\u2009ng\/mL IL\u20104, IL\u201010, or each in combination with 1\u2009ng\/mL IL\u20101\u03b2 stimulation. The role of IL\u20104 and IL\u201010 in the IVD was evaluated using immunohistochemistry, gene expression, and Luminex multiplex immunoassay proteomics (73 secreted) and phosphoproteomics (21 phosphorylated proteins).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>IL\u20104, IL\u20104R, and IL\u201010R expression and localization in human cartilage endplate tissue were demonstrated for the first time. No significant gene expression changes were noted under IL\u20104 or IL\u201010 stimulation. However, IL\u20101\u03b2 stimulation significantly increased <jats:italic>MMP3<\/jats:italic>, <jats:italic>COX2<\/jats:italic>, <jats:italic>TIMP1<\/jats:italic>, and TRPV4 expression in NP cells from trauma IVDs. Combined IL\u20104 and IL\u20101\u03b2 treatment induced a significant increase in protein secretion of IL\u20101\u03b1, IL\u20107, IL\u201016, IL\u201017F, IL\u201018, IFN\u03b3, TNF, ST2, PROK1, bFGF2, and stem cell factor exclusively in NP cells from degenerated IVDs. Conversely, the secretome profile of explants revealed an IL\u20104\u2013mediated decrease in CXCL13 following treatment with IL\u20101\u03b2. Combined IL\u201010 and IL\u20101\u03b2 treatment increased neurotrophic growth factor secretion compared with IL\u201010 baseline.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The NP cell phenotype affects the pleiotropic role of IL\u20104, which can induce a pro\u2010inflammatory response in the presence of catabolic stimuli and enhance the effects of IL\u20101\u03b2 in degenerated IVDs. Environmental factors, including 3D culture and hypoxia, may alter IL\u20104's role. Finally, IL\u201010's potential neurotrophic effects under catabolic stimuli warrant further investigation to clarify its role in IVD degeneration.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jsp2.70048","type":"journal-article","created":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T10:27:39Z","timestamp":1739269659000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Ex Vivo and In\u00a0Vitro Proteomic Approach to Elucidate the Relevance of <scp>IL<\/scp>\u20104 and <scp>IL<\/scp>\u201010 in Intervertebral Disc Pathophysiology"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6858-8213","authenticated-orcid":false,"given":"Paola","family":"Bermudez\u2010Lekerika","sequence":"first","affiliation":[{"name":"Tissue Engineering for Orthopaedics and Mechanobiology, Bone and Joint Program, Department for BioMedical Research (DBMR), Faculty of Medicine University of Bern  Bern 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