Abstract
Background Rheumatoid arthritis (RA) is a chronic condition that manifests as inflammation of synovial joints, leading to joint destruction and deformity. Methods We identified single-cell RNA-seq data of synovial fibroblasts from RA and osteoarthritis (OA) patients in GSE109449 dataset. RA- and OA-specific cellular subpopulations were identified, and enrichment analysis was performed. Further, key genes for RA and OA were obtained by combined analysis with differentially expressed genes (DEGs) between RA and OA in GSE56409 dataset. The diagnostic role of key genes for RA was predicted using receiver operating characteristic (ROC) curve. Finally, we identified differences in immune cell infiltration between RA and OA patients, and utilized flow cytometry, qRT-PCR, and Western blot were used to examine the immune cell and key genes in RA patients. Results The cluster 0 matched OA and cluster 3 matched RA and significantly enriched for neutrophil-mediated immunity and ECM receptor interaction, respectively. We identified 478 DEGs. In the top 20 degrees of connection in the PPI network, the key genes for RA were obtained by comparing with the gene markers of cluster 0 and cluster 3, respectively. ROC curve showed that CCL2 and MMP13 might be diagnostic markers for RA. We found aberrant levels of CD8+T, neutrophil, and B cells in RA fibroblasts, which were validated in clinical samples. Importantly, we also validated the differential expression of key genes between RA and OA. Conclusion High expression of CCL2 and MMP13 in RA may be a diagnostic and therapeutic target.
Highlights
Rheumatoid arthritis (RA) is a chronic inflammatory disease that affects joint synovial tissue, causing joint pain and disability [1]
GSE56409 included gene expression profile of fibroblasts which were isolated from synovium, bone marrow, or skin tissue samples of 12 rheumatoid arthritis patients and 6 osteoarthritis patients at the time of knee or hip replacement surgery based on GPL570 of array [17]
We found that the levels of CD8+T cells and neutrophil were significantly higher in RA patients than in OA patients, while the levels of B cells were significantly decreased (Figure 6(d))
Summary
Rheumatoid arthritis (RA) is a chronic inflammatory disease that affects joint synovial tissue, causing joint pain and disability [1]. RA is characterized by infiltration of synovium with inflammatory cells, hyperplasia of synovial fibroblasts, and progressive inflammation of the joint, leading to cartilage destruction, bone erosion, and disability [2, 3]. Within 10 years of RA onset, at least 50% of patients in developed countries are unable to take full-time jobs, probably due to the resulting disability [5]. We identified single-cell RNA-seq data of synovial fibroblasts from RA and osteoarthritis (OA) patients in GSE109449 dataset. Key genes for RA and OA were obtained by combined analysis with differentially expressed genes (DEGs) between RA and OA in GSE56409 dataset. We identified 478 DEGs. In the top 20 degrees of connection in the PPI network, the key genes for RA were obtained by comparing with the gene markers of cluster 0 and cluster 3, respectively. High expression of CCL2 and MMP13 in RA may be a diagnostic and therapeutic target
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
