Targets and Potential Mechanism of Chondroitin Sulfate A-selenium Nanoparticle on Kashin-Beck Disease Chondrocytes

Kashin-Beck disease (KBD) is a chronic and deformable osteoarthropathy linked to low selenium. Limited cartilage regeneration poses challenges for its treatment. Previous studies have found that chondroitin sulfate A-selenium nanoparticle (CSA-SeNP) protects chondrocytes. This study used label-free LC–MS/MS quantitative proteomics to identify differentially expressed proteins and pathways in KBD chondrocytes post-CSA-SeNP treatment. Western blot (WB) was used to verify the key differential proteins, and transmission electron microscopy (TEM) was used to observe the ultrastructure of chondrocytes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed proteins mainly involved in RNA processing, translation, peptide biosynthesis, gene expression, rRNA metabolism, and ribonucleoprotein complex biogenesis. Notably, 121 proteins were up-regulated, 27 down-regulated, and 117 specifically expressed in the CSA-SeNP group. Enriched KEGG pathways included ribosome biogenesis, mRNA surveillance, endoplasmic reticulum protein processing, and endocytosis. Proteins related to autophagy, ER stress, cell homeostasis, protein processing and transport, including PELO, WES1, PLAA, RRBP1, ARC1B, ARFGAP2, and SH3KBP1, were significantly up-regulated in the CSA-SeNP group. In conclusion, our results demonstrated that CSA-SeNP may exert protective effects on chondrocytes in adult patients with KBD mainly through the regulation of target proteins and pathways related to ribosome biogenesis, mRNA surveillance, endoplasmic reticulum protein processing, endocytosis, autophagy, ER stress, and cell homeostasis. Further studies with larger sample size and in vivo to identify, screen and verify the regulatory effects of target proteins and pathways may provide more information for elucidating the mechanism of CSA-SeNP in the treatment of KBD.