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Hyperglycemia resulting from diabetes mellitus induces advanced glycation end products (AGEs) accumulation in nucleus pulposus cells, leading to IVDD. Mitigating AGEs accumulation is a novel promising strategy for IVDD management. In our study, palladium nanoparticles (Pd NPs) preferentially colocalized within the endoplasmic reticulum and efficiently degraded AGEs via valosin\u2010containing protein (VCP)\u2010mediated autophagy pathways. Pd NPs promoted the ATPase activity of VCPs, upregulated microtubule\u2010associated proteins 1A\/1B light chain 3 (LC3) expression, and increased AGEs\u2010degrading autophagosome production. They ameliorated mitochondrial function, relieved endoplasmic reticulum stress, and counteracted the detrimental oxidative stress microenvironment in a high\u2010glucose\/high\u2010fat\u2010induced nucleus pulposus cell degeneration model. Consequently, Pd NPs effectively rescued nucleus pulposus cell degeneration in vitro, restored disc height and partially recovered the degenerated phenotype of IVDD in vivo. We provide novel insights regarding IVDD management by targeting AGEs degradation, showing potential for clinical practice.<\/jats:p>","DOI":"10.1002\/exp.20230174","type":"journal-article","created":{"date-parts":[[2025,1,17]],"date-time":"2025-01-17T05:46:48Z","timestamp":1737092808000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Palladium Nanoparticles Degrade Advanced Glycation End Products via Valosin\u2010Containing Protein Mediated Autophagy to Attenuate High\u2010Glucose\/High\u2010Fat\u2010Induced Intervertebral Disc Degeneration"],"prefix":"10.1002","volume":"5","author":[{"given":"Xiao","family":"Yang","sequence":"first","affiliation":[{"name":"Shanghai Key Laboratory of Orthopedic Implants Department of Orthopedics Ninth People's Hospital Shanghai Jiao Tong University School of Medicine Shanghai 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