Nonhistone Protein Acetylation Reprograms the ECM-Receptor Interaction Pathway: Multiomics Profiling of Cartilage Degeneration in Rat Models of Osteoarthritis.

Nonhistone acetylation is a key epigenetic mechanism in osteoarthritis (OA), but its specific role in cartilage degeneration remains unclear. Here, we integrated transcriptomics, proteomics, and acetyl-proteomics to systematically analyze molecular changes in rat OA cartilage. Multiomics coenrichment identified the ECM-receptor interaction pathway as the core target, reprogrammed by increased acetylation of Fn1, Tnc, and Itgb1. Using 113 machine-learning strategies, we identified 11 core diagnostic genes, with Wisp3 showing the highest efficacy validated in independent data sets. In vitro experiments and single-cell RNA-seq confirmed that Wisp3 downregulation disrupts ECM homeostasis. This study reveals that nonhistone acetylation drives OA by reprogramming the ECM-receptor interaction pathway and provides novel early diagnostic biomarkers.