{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T17:41:00Z","timestamp":1788802860407,"version":"build-2803163510"},"reference-count":30,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2022,1,27]],"date-time":"2022-01-27T00:00:00Z","timestamp":1643241600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Gene Medicine"],"published-print":{"date-parts":[[2022,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>This study was designed to verify whether enhancer of zeste homolog 2 (EZH2) affects intervertebral disc degeneration (IVDD) development through regulation of microRNA (miR)\u2010129\u20105p\/MAPK1.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Initially, we collected lumbar nucleus pulposus (NP) tissue samples from patients with juvenile idiopathic scoliosis (<jats:italic>n<\/jats:italic>\u2009=\u200914) and IVDD (<jats:italic>n<\/jats:italic>\u2009=\u200934). We measured the expression of related genes in clinical IVDD tissues and a lipopolysaccharide (LPS)\u2010induced NP cell model. After loss\u2010 and gain\u2010of\u2010function assays, NP cell proliferation and senescence were examined. The targeting relationship between miR\u2010129\u20105p and MAPK1 was explored by dual luciferase reporter gene and RNA immunoprecipitation (RIP) assays. The enrichment of EZH2 and H3K27me3 in miR\u2010129\u20105p promoter was verified by chromatin immunoprecipitation (ChIP). Finally, an IVDD rat model was established to test the effects of transduction with lentiviral vector carrying miR\u2010129\u20105p agomir and\/or oe\u2010EZH2 in vivo.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>miR\u2010129\u20105p was underexpressed, and EZH2 and MAPK1 levels were overexpressed in lumbar nucleus pulposus from human IVDD patients and in LPS\u2010induced NP cells. miR\u2010129\u20105p overexpression or silencing of MAPK1 promoted proliferation of NP cells, while inhibiting their senescence. EZH2 inhibited miR\u2010129\u20105p through H3K27me3 modification in the miR\u2010129\u20105p promoter. miR\u2010129\u20105p could target the downregulation of MAPK1 expression. EZH2 overexpression increased the release of inflammatory factors and cell senescence factors, which was reversed by miR\u2010129\u20105p agomir in vivo.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Taken together, EZH2 inhibits miR\u2010129\u20105p through H3K27me3 modification, which upregulates MAPK1, thereby promoting the development of IVDD.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jgm.3395","type":"journal-article","created":{"date-parts":[[2021,10,20]],"date-time":"2021-10-20T22:00:41Z","timestamp":1634767241000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["EZH2 upregulates the expression of MAPK1 to promote intervertebral disc degeneration via suppression of miR\u2010129\u20105p"],"prefix":"10.1002","volume":"24","author":[{"given":"Meng","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Orthopedic Surgery The First Affiliated Hospital of Soochow University  Suzhou Jiangsu P. R. China"},{"name":"Department of Orthopedic Surgery Tengzhou Central People's Hospital  Tengzhou Shandong P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang\u2010Jun","family":"He","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Affiliated Danyang Hospital of Nantong University, The People's Hospital of Danyang  Danyang Jiangsu P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Tengzhou Central People's Hospital  Tengzhou Shandong P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mao\u2010Jie","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Tengzhou Central People's Hospital  Tengzhou Shandong P. R. 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