Prediction of potential biomarkers and therapeutic targets of copper death in osteoarthritis

Abstract

Abstract Osteoarthritis (OA) is a common degenerative joint disease characterized by articular cartilage destruction and synovial damage. The immune system has an impact on the development of OA. The infiltration of immune cells will cause the autoimmune reaction of osteoarthritis and disrupt the immune equilibrium in bone tissue. Recent studies have demonstrated that copper is crucial in regulating the immune system. Copper can also mediate cell death through a new cell death program by targeting the tricarboxylic acid cycle (TCA) circulating protein. However, no research has been conducted on the copper death gene regulation of OA immune response.The gene expression profiles—GSE55235, GSE82107, and GSE206848—were obtained from the GEO database. A total of 24 healthy and 27 OA joint synovial samples were screened for differentially expressed genes (DEGs) in combination with copper death-related genes and immune-related genes to conduct subsequent analyses.We have selected seven genes—NAMPT, EGFR, ADM, APOD, CD28, CXCL12, and MMP9—as potentially essential marker genes to regulate copper death. These marker genes are enriched in autophagy, lysosome, apoptosis, immune response, polysaccharide synthesis and metabolism, and signaling pathways of related diseases. The proportion of NKT cells in OA samples was significantly higher than that in the control group, whereas neutrophil expression was significantly lower than that in the healthy group. Finally, RT-PCR confirmed that the expressions of NAMPT and EGFR in the disease group were lower than those in the control group.We developed and validated the immune copper death DEGs model, which can accurately diagnose and characterize the biological changes of OA. Seven marker genes may also be potential targets of immunomodulatory therapy, including NAMPT and EGFR, which play an essential role in bone and joint, thereby providing prediction and theoretical support for the regulatory mechanism of copper death in osteoarthritis.