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While inhibition of cellular senescence can prevent age\u2010related diseases, the understanding of the regulators governing cartilage senescence and the potential for senolytic intervention remains limited. Here, in vitro and in vivo results are reported, demonstrating for the first time that the transcriptional regulator, ZMIZ1, is upregulated in aged and OA cartilage, and that it acts through GATA4 to accelerate chondrocyte senescence and trigger cartilage deterioration. Furthermore, it is shown that K\u20107174 interferes with the ZMIZ1\u2010GATA4 interaction and effectively hampers cartilage senescence and OA. It is proposed that inhibition of the ZMIZ1\u2010GATA4 axis could be a valuable strategy for eliminating senescent chondrocytes and impeding OA development and that the relevant inhibitor, K\u20107174, could potentially be developed as a senolytic drug for managing cartilage senescence and age\u2010related degeneration.<\/jats:p>","DOI":"10.1002\/advs.202404311","type":"journal-article","created":{"date-parts":[[2025,3,8]],"date-time":"2025-03-08T13:00:40Z","timestamp":1741438840000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Blockade of ZMIZ1\u2010GATA4 Axis Regulation Restores Youthfulness to Aged Cartilage"],"prefix":"10.1002","volume":"12","author":[{"given":"Jiho","family":"Nam","sequence":"first","affiliation":[{"name":"Department of Biological Science Sungkyunkwan University  Suwon 16419 Republic of 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