{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T12:09:50Z","timestamp":1785326990085,"version":"3.55.0"},"reference-count":44,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T00:00:00Z","timestamp":1783296000000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunity Inflam &amp;amp; Disease"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study investigated the expression profile of Thrombospondin\u20104 (THBS4) in intervertebral disc degeneration (IDD) and clarify its regulatory role in lipopolysaccharide (LPS)\u2010induced apoptosis and inflammation in nucleus pulposus cells (NPCs) via the phosphatidylinositol 3\u2010kinase (PI3K)\/protein kinase B (AKT) pathway.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>IDD\u2010related differentially expressed genes were screened through the integration of GeneCards and the Gene Expression Omnibus (GEO) database (GSE186542), followed by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis to explore potential signaling mechanisms. An in vitro inflammatory injury model was established using LPS\u2010stimulated NPCs. The effects of THBS4 overexpression on cell proliferation, apoptosis, inflammatory cytokine secretion, and extracellular matrix protein expression were evaluated using reverse transcription\u2010quantitative polymerase chain reaction (RT\u2010qPCR), western blotting, 5\u2010ethynyl\u20102\u2032\u2010deoxyuridine (EdU) assay, flow cytometry, and enzyme\u2010linked immunosorbent assay (ELISA). Additionally, the involvement of the PI3K\/AKT pathway in mediating THBS4\u2010related effects was confirmed using the PI3K inhibitor LY294002.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Bioinformatics analysis revealed that THBS4 was significantly downregulated in IDD and was closely linked to the PI3K\/AKT pathway. Functional assays demonstrated that overexpression of THBS4 markedly enhanced NPCs proliferation, suppressed apoptosis, reduced the secretion of tumour necrosis factor alpha (TNF\u2010\u03b1), interleukin\u20101beta (IL\u20101\u03b2) and IL\u20106, and increased the expression of IL\u201010, Aggrecan, and Collagen type II. These protective effects were accompanied by activation of the PI3K\/AKT pathway and were significantly reversed by LY294002 treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>THBS4 alleviated LPS\u2010induced damage in NPCs through the activation of the PI3K\/AKT pathway, exerting anti\u2010apoptotic and anti\u2010inflammatory effects; the specific upstream molecular mechanism of PI3K\/AKT activation by THBS4 requires further investigation. These findings suggested that THBS4 may serve as a potential therapeutic target for IDD treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/iid3.70484","type":"journal-article","created":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T06:39:20Z","timestamp":1783406360000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Thrombospondin\u20104 Regulates Lipopolysaccharide\u2010Induced Apoptosis and Inflammation in Nucleus Pulposus Cells via the Phosphatidylinositol 3\u2010Kinase\/Protein Kinase B Pathway"],"prefix":"10.1002","volume":"14","author":[{"given":"Yang","family":"Shu","sequence":"first","affiliation":[{"name":"Department of Orthopedics The Sixth Hospital of Wuhan, Affiliated Hospital of Jianghan University Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunhua","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Hemodialysis Wuhan 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