Nonhistone Protein Acetylation Reprograms the ECM-Receptor Interaction Pathway: Multiomics Profiling of Cartilage Degeneration in Rat Models of Osteoarthritis
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引用次数: 0
Abstract
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.
期刊介绍：
Journal of Proteome Research publishes content encompassing all aspects of global protein analysis and function, including the dynamic aspects of genomics, spatio-temporal proteomics, metabonomics and metabolomics, clinical and agricultural proteomics, as well as advances in methodology including bioinformatics. The theme and emphasis is on a multidisciplinary approach to the life sciences through the synergy between the different types of "omics".
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