{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T09:58:34Z","timestamp":1753869514868,"version":"3.41.2"},"reference-count":49,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,4,8]],"date-time":"2025-04-08T00:00:00Z","timestamp":1744070400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2024A1515013042"],"award-info":[{"award-number":["2024A1515013042"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["JOR Spine"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Intervertebral disk (IVD) degeneration is associated with lower back pain and aging; however, the mechanisms underlying age\u2010related changes and the changes in macrophage polarization in aging intervertebral disks require further elucidation. The aim of this study was to evaluate changes in macrophages, the differential expression of senescence genes, and their relationship with hub genes in IVDs during aging in mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Twenty\u2010eight male wild C57 mice aged 4\u2009weeks were divided into two groups. Four mice per group were selected for high\u2010throughput sequencing and 10 for tail IVD immunohistochemical analysis. Adult and aged mouse IVD specimens were stained with hematoxylin\u2013eosin, Fast Green, and Alcian Blue to determine collagen (Col) 1, Col2, proteoglycan, P16, P21, P53, CD11b, CD86, CD206, IL\u20101, TGF\u2010\u03b2, and IL\u20104 expression. High\u2010throughput sequencing was performed on adult and aged mouse IVD tissues.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Aged mouse IVDs showed reduced height and marked degeneration, with decreased Col2 and proteoglycan expression and increased Col1 expression. The expression of senescence markers, senescence\u2010associated IL\u20101, TGF\u2010\u03b2, and IL\u20104, and macrophage\u2010related markers, CD11b, CD86, and CD206, increased markedly with age. High\u2010throughput sequencing revealed 1975 differentially expressed genes in adult and aged mice, with 797 genes showing upregulated expression (top five: <jats:italic>Kcna7<\/jats:italic>, <jats:italic>Mmp9<\/jats:italic>, <jats:italic>Panx3<\/jats:italic>, <jats:italic>Myl10<\/jats:italic>, and <jats:italic>Bglap<\/jats:italic>) and 1178 showing downregulated expression (top five: <jats:italic>Srd5a2<\/jats:italic>, <jats:italic>Slc38a5<\/jats:italic>, <jats:italic>Gm47283<\/jats:italic>, <jats:italic>Npy<\/jats:italic>, and <jats:italic>Pcdh8<\/jats:italic>). Gene Ontology and pathway enrichment analyses highlighted aging\u2010related cellular components, biological processes, and metabolic pathways. The identified hub genes included <jats:italic>Cox5a<\/jats:italic>, <jats:italic>Ndufs6<\/jats:italic>, and <jats:italic>Ndufb9<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Disk senescence and reduced height in aged mice are linked to upregulated expression of senescence\u2010associated phenotypes and macrophage polarization markers. These findings suggest that macrophages and differential gene expression play key roles in age\u2010related IVD degeneration, indicating that they can be used as potential targets for therapeutic intervention.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jsp2.70061","type":"journal-article","created":{"date-parts":[[2025,4,8]],"date-time":"2025-04-08T15:42:53Z","timestamp":1744126973000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Macrophage Changes and High\u2010Throughput Sequencing in Aging Mouse Intervertebral Disks"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-1284-8429","authenticated-orcid":false,"given":"Wei","family":"Wang","sequence":"first","affiliation":[{"name":"Chongqing Tongnan Hospital of Traditional Chinese Medicine  Chongqing People's Republic of China"},{"name":"Department of Orthopaedic Surgery Gaozhou People's Hospital  Gaozhou Guangdong Province People's 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Orthopaedic Surgery Gaozhou People's Hospital  Gaozhou Guangdong Province People's Republic of China"},{"name":"Graduate School of Guangdong Medical University  ZhanJiang Guangdong People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao\u2010Chuan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery Gaozhou People's Hospital  Gaozhou Guangdong Province People's Republic of 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