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Updated: Apr 30, 2026
Software-Assisted Quantitative Measurement of Osteoarthritic Subchondral Bone Thickness
Published on: March 18, 2022
Exploring immune modulation in osteoarthritis: identifying key biomarkers and the role of PTPRC in regulating immune
Zhengyao Zhang1,2, Yilin Wang1,3, Zhiwen Tan4
1Women and Children's Hospital of Dalian University of Technology, Dalian, China.
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, in vitro validation confirmed key findings.
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. In vitro experiments demonstrate that one of the hub genes-PTPRC-alleviates the deterioration of OA through three levels. Virtual knockout in Natural Killer (NK) cells further confirms that PTPRC influences OA by regulating the immune microenvironment.
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.
Insights
This study identifies three key biomarkers for osteoarthritis (OA) and reveals that protein tyrosine phosphatase receptor type C (PTPRC) alleviates OA progression by modulating the immune microenvironment. This offers a new therapeutic avenue for OA treatment.
Area of Science:
- Immunology
- Genomics
- Biomarker Discovery
Background:
- Osteoarthritis (OA) is a prevalent degenerative joint disease causing chronic pain and disability.
- Molecular mechanisms of OA pathogenesis, especially immune microenvironment modulation, are not fully understood.
- This study investigates immune-related OA progression and potential diagnostic/therapeutic biomarkers.
Purpose of the Study:
- To identify key genes and pathways involved in osteoarthritis (OA) pathogenesis.
- To explore the role of the immune microenvironment in OA progression.
- To discover novel biomarkers for OA diagnosis and therapeutic intervention.
Main Methods:
- Analysis of gene expression data from the GEO database to identify differentially expressed genes (DEGs).
- Weighted gene co-expression network analysis (WGCNA) to identify OA-associated gene modules.
- Protein-protein interaction (PPI) network, XGBoost, and Random Forest analyses to pinpoint hub genes.
- Immune cell infiltration analysis, single-cell sequencing, Mendelian randomization (MR), and Western blotting (WB) for validation.
- In vitro experiments to confirm key findings, including the role of PTPRC.
Main Results:
- Identified 1,171 upregulated DEGs and 25 co-expression modules, with the turquoise module strongly linked to OA.
- Pinpointed three hub genes: protein tyrosine phosphatase receptor type C (PTPRC), CX3CR1, and ITGB2, through network and machine learning analyses.
- PTPRC was found to alleviate OA deterioration and influence OA by regulating the immune microenvironment, particularly in Natural Killer (NK) cells.
Conclusions:
- Identified PTPRC, CX3CR1, and ITGB2 as promising biomarkers for osteoarthritis.
- Confirmed PTPRC's pivotal role in alleviating OA progression via immunomodulation.
- Proposed a novel intervention strategy for OA combining tissue engineering with immunomodulatory therapy.
