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This study finds that the absence of BCL2\/adenovirus E1B 19\u00a0kDa interacting protein 3 (BNIP3) is associated with senescence\u2010related NPC degeneration, disrupting mitochondrial quality control. Bone marrow mesenchymal stem cells (BMSCs) have multidirectional differentiation potential and produce extracellular vesicles containing cellular activators. Therefore, in this study, BMSCs are induced under hypoxic stimulation to deliver BNIP3\u2010rich extracellular vesicles to NPCs, thereby alleviating aging\u2010associated mitochondrial autophagic flux, promoting damaged mitochondrial clearance, and restoring mitochondrial quality control. Mechanistically, BNIP3 is shown to interact with the membrane\u2010bound protein annexin A2 (ANXA2), enabling the liberation of the transcription factor EB (TFEB) from the ANXA2\u2010TFEB complex, promoting TFEB nuclear translocation, and regulating autophagy and lysosomal gene activation. Furthermore, a rat model of IVDD is established and verified the in vivo efficacy of the exosomes in repairing disc injuries, delaying NPC aging, and promoting extracellular matrix (ECM) synthesis. In summary, hypoxia\u2010induced BMSC exosomes deliver BNIP3\u2010rich vesicles to alleviate disc degeneration by activating the mitochondrial BNIP3\/ANXA2\/TFEB axis, providing a new target for IVDD treatment.<\/jats:p>","DOI":"10.1002\/advs.202404275","type":"journal-article","created":{"date-parts":[[2024,7,8]],"date-time":"2024-07-08T03:25:31Z","timestamp":1720409131000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":82,"title":["Hypoxia\u2010Preconditioned BMSC\u2010Derived Exosomes Induce Mitophagy via the BNIP3\u2013ANAX2 Axis to Alleviate Intervertebral Disc Degeneration"],"prefix":"10.1002","volume":"11","author":[{"given":"Yuxin","family":"Jin","sequence":"first","affiliation":[{"name":"Department of Orthopaedics Key Laboratory of Structural Malformations in Children of Zhejiang Province Key Laboratory of Orthopaedics of Zhejiang Province The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou 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