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However, no effective disease\u2010modifying therapies presently exist for IDD or its related pathologies. Single\u2010cell sequencing analyses reveal progressive M1 macrophage polarization in NP cells correlating with IDD severity, underscoring the therapeutic imperative for dual\u2010targeting agents addressing both inflammatory dysregulation and matrix homeostasis. \u03b2\u2010mangostin (\u03b2_Man) is screened to be proven to possess potential therapeutic effects in alleviating IDD. \u03b2_Man possesses anti\u2010inflammatory capabilities, which include remodeling the homeostasis of the extracellular matrix, regulating macrophage polarization, and inhibiting apoptosis in the nucleus pulposus. TET2\u2010Prkcg exerts significant regulatory functions downstream of \u03b2_Man. Mechanically, \u03b2_Man mediated reduction of TET2 maintains the DNA methylation of Prkcg rather than hydroxymethylation, which promotes mitophagy and alleviates the inflammatory microenvironment. \u03b2_Man represents a promising novel therapeutic strategy for IDD treatment. The TET2\u2010Prkcg axis emerges as a novel therapeutic target for IDD treatment.<\/jats:p>","DOI":"10.1002\/advs.202505077","type":"journal-article","created":{"date-parts":[[2025,6,25]],"date-time":"2025-06-25T09:15:36Z","timestamp":1750842936000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["\u03b2\u2010Mangostin Attenuates TET2\u2010Mediated DNA Demethylation of Prkcg in the Prevention of Intervertebral Disc Degeneration"],"prefix":"10.1002","volume":"12","author":[{"given":"Xiangzhen","family":"Kong","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery Qilu Hospital Cheeloo College of Medicine Shandong University  Jinan Shandong 250012 P. R. China"},{"name":"The First Clinical College of Shandong University  Jinan Shandong 250012 P. R. 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