Palladium Nanoparticles Degrade Advanced Glycation End Products via Valosin‐Containing Protein Mediated Autophagy to Attenuate High‐Glucose/High‐Fat‐Induced Intervertebral Disc Degeneration

• Published in: Exploration (Beijing, China) Vol. 5; no. 2; pp. 20230174 - n/a
• Main Authors: Yang, Xiao, Cao, Xiankun, Wang, Xin, Guo, Jiadong, Yang, Yangzi, Lu, Liqiang, Zhang, Pu, Yang, Huan, Rong, Kewei, Zhou, Tangjun, Hao, Yongqiang, Zhao, Jie, Fu, Jingke, Zhang, Kai
• Format: Journal Article
• Language: English
• Published: China John Wiley & Sons, Inc 01.04.2025; John Wiley and Sons Inc; Wiley
• Subjects: Accumulation; advanced glycation end products; Advanced glycosylation end products; Autophagy; Back pain; Degeneration; Degenerative disc disease; Diabetes mellitus; Endoplasmic reticulum; Global health; Glucose; high‐glucose/high‐fat; Hyperglycemia; intervertebral disc degeneration; Intervertebral discs; Low back pain; Microenvironments; Microscopy; Musculoskeletal diseases; Nanoparticles; Nuclei (cytology); Nucleus pulposus; Oxidative stress; Palladium; palladium nanoparticles; Phenotypes; Proteins; Public health; intervertebral disc degeneration; palladium nanoparticles; advanced glycation end products; nucleus pulposus; high‐glucose/high‐fat
• ISSN: 2766-8509; 2766-2098; 2766-2098
• DOI: 10.1002/EXP.20230174

ABSTRACT Intervertebral disc degeneration (IVDD) is a chronic musculoskeletal disorder causing lower back pain, imposing a considerable burden on global health. 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‐containing protein (VCP)‐mediated autophagy pathways. Pd NPs promoted the ATPase activity of VCPs, upregulated microtubule‐associated proteins 1A/1B light chain 3 (LC3) expression, and increased AGEs‐degrading autophagosome production. They ameliorated mitochondrial function, relieved endoplasmic reticulum stress, and counteracted the detrimental oxidative stress microenvironment in a high‐glucose/high‐fat‐induced 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. Illustration of Pd NP‐mediated rescue of HGHF (or advanced glycation end products [AGEs])‐induced IVD degeneration by targeting AGEs degradation. Pd NPs promote the ATPase activity of VCP and upregulate autophagosome formation to degrade AGEs. Consequently, Pd NPs alleviate the oxidative and ER stress, protect the structure and function of mitochondria, and eventually facilitate IVDD mitigation. Created with BioRender.com (Agreement No. JU26337Q4Q).