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The development of IVDD is closely associated with abnormal epigenetic changes, suggesting that IVDD progression may be controlled by epigenetic mechanisms. Consequently, this study aimed to investigate the role of epigenetic regulation, including DNA methyltransferase 3a (DNMT3a)\u2010mediated methylation and peroxisome proliferator\u2010activated receptor \u03b3 (PPAR\u03b3) inhibition, in IVDD development. The expression of DNMT3a and PPAR\u03b3 in early and late IVDD of nucleus pulposus (NP) tissues was detected using immunohistochemistry and western blotting analyses. Cellularly, DNMT3a inhibition significantly inhibited IL\u20101\u03b2\u2010induced apoptosis and extracellular matrix (ECM) degradation in rat NP cells. Pretreatment with T0070907, a specific inhibitor of PPAR\u03b3, significantly reversed the anti\u2010apoptotic and ECM degradation effects of DNMT3a inhibition. Mechanistically, DNMT3a modified PPAR\u03b3 promoter hypermethylation to activate the nuclear factor\u2010\u03baB (NF\u2010\u03baB) pathway. DNMT3a inhibition alleviated IVDD progression. Conclusively, the results of this study show that DNMT3a activates the NF\u2010\u03baB pathway by modifying PPAR\u03b3 promoter hypermethylation to promote apoptosis and ECM degradation. Therefore, we believe that the ability of DNMT3a to mediate the PPAR\u03b3\/NF\u2010\u03baB axis may provide new ideas for the potential pathogenesis of IVDD and may become an attractive target for the treatment of IVDD.<\/jats:p>","DOI":"10.1111\/jcmm.18048","type":"journal-article","created":{"date-parts":[[2023,11,21]],"date-time":"2023-11-21T23:50:52Z","timestamp":1700610652000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["<scp>DNMT3a<\/scp>\u2010mediated methylation of <scp>PPAR\u03b3<\/scp> promote intervertebral disc degeneration by regulating the <scp>NF\u2010\u03baB<\/scp> pathway"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-8665-9263","authenticated-orcid":false,"given":"Peng","family":"Cheng","sequence":"first","affiliation":[{"name":"Department of Emergency Medicine Lanzhou University Second Hospital  Lanzhou Gansu PR China"},{"name":"Department of 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