ArticleFrontiers in immunology2026
Exploring immune modulation in osteoarthritis: identifying key biomarkers and the role of PTPRC in regulating immune microenvironment for therapeutic intervention.
Article in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Osteoarthritis (OA) is widely recognized as the most prevalent degenerative disorder affecting the joints, representing a major contributor to chronic pain and disability. Despite its high burden, the molecular mechanisms underlying OA pathogenesis remain poorly understood, particularly in the context of immune microenvironment modulation. This study explores the immune-related OA progression mechanisms and investigates potential biomarkers to aid diagnosis and therapeutic intervention. Methods: Gene expression data from the GEO database were analyzed, differentially expressed genes (DEGs) and OA-associated gene modules were identified using the LIMMA package in combination with weighted gene co-expression network analysis (WGCNA). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted on intersecting genes, which were analyzed using the protein-protein interaction network, XGBoost, and Random Forest, identifying core genes. Subsequently, immune cell infiltration was determined through immune cell infiltration analysis and single-cell sequencing analysis. Next, core genes were validated using Mendelian randomization (MR) and Western blotting (WB). Finally, Results: A total of 1,171 upregulated DEGs were identified. WGCNA analysis delineated 25 co-expression modules, and the turquoise module emerged as the most strongly related to OA. The PPI network, XGBoost, and Random Forest analysis pinpointed three hub genes: protein tyrosine phosphatase receptor type C (PTPRC), C-X3-C Motif Chemokine Receptor 1 (CX3CR1) and Integrin Subunit Beta 2 (ITGB2). Immune cell infiltration analysis indicates that these key genes exhibit significant associations with immune cells, while single-cell sequencing and GSEA enrichment analysis further suggested their involvement in inflammatory pathways and immune activation. Conclusions: This study identified three promising biomarkers in OA and certificated that PTPRC plays a pivotal role in alleviating OA progression through immunomodulation, offering a novel intervention pathway for tissue engineering combined with immunomodulatory therapy in OA.
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