Exploration of differential expression and biological significance of amino acid metabolism genes in osteoarthritis

TL;DR

This study identifies genes involved in amino acid metabolism that are linked to osteoarthritis, offering potential targets for early detection and treatment.

Contribution

The study discovers key amino acid metabolism-related genes and develops accurate diagnostic models for osteoarthritis.

Findings

169 amino acid metabolism-related differentially expressed genes were identified in osteoarthritis.

Genes like SLC2A4, MTHFD2, and WNT5B show potential as therapeutic targets and diagnostic markers.

Diagnostic models using LASSO and SVM achieved high accuracy with an area under the curve > 0.9.

Abstract

Osteoarthritis (OA) is a widespread disorder affecting joints, recognized for cartilage wear and inflammatory responses, which substantially affects patients’ quality of life. This research aim to discover amino acid metabolism-related differentially expressed genes (AAMRDEGs) and clarify their functions in OA pathogenesis.

Herein, we conducted an analysis of combined GEO datasets (GSE55457, GSE55235, and GSE12021), identifying 169 AAMRDEGs and indicating their importance in chondrocyte function and inflammation. Furthermore, significant correlations were observed between various immune cell types, underscoring the intricate function of the immune system in OA. Thereafter, we developed highly accurate diagnostic models using LASSO regression and SVM methodologies, achieving an area under the curve > 0.9. Protein-protein interaction analysis revealed significant interactions among MTHFD2, PPP1R15A, SLC2A4, and WNT5B, with their expression levels corroborated using single-cell datasets, highlighting the potential therapeutic targets. To confirm the presence of these hub AAMRGs, real-time polymerase chain reaction and immunohistochemistry were employed.

We identified 2,115 DEGs between OA and control groups, with 1,062 upregulated and 1,053 downregulated. Enrichment analysis linked AAMRDEGs to amino acid catabolism and multiple KEGG pathways, indicating their importance in chondrocyte function and inflammation. Furthermore, significant correlations were observed between various immune cell types, underscoring the intricate role of the immune system in OA. Subsequently, we developed highly accurate diagnostic models using LASSO regression and SVM methodologies, achieving an area under the curve > 0.9. Protein-protein interaction analysis revealed significant interactions among MTHFD2, PPP1R15A, SLC2A4, and WNT5B, with their expression levels corroborated using single-cell datasets, highlighting the potential therapeutic targets. Real-time polymerase chain reaction and immunohistochemistry were used to validate the expression of these hub amino acid metabolism-related genes.

This investigation presents a detailed evaluation of AAMRGs in OA, highlighting their roles in disease pathogenesis and offering new insights for therapeutic research. Key genes SLC2A4, MTHDF2, and WNT5B might function as markers for early identification and personalized OA treatment.

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