Skip to main page content
U.S. flag

An official website of the United States government

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comparative Study
. 2024 Sep 20;22(1):851.
doi: 10.1186/s12967-024-05643-4.

Similarities and differences between osteoarthritis and rheumatoid arthritis: insights from Mendelian randomization and transcriptome analysis

Zhixiang Zhang #  1 , Zhiqiang Shao #  2 , Zonghan Xu  3 , Jiaqian Wang  4
Affiliations
Comparative Study

Similarities and differences between osteoarthritis and rheumatoid arthritis: insights from Mendelian randomization and transcriptome analysis

Zhixiang Zhang et al. J Transl Med. .

Abstract

Background: Osteoarthritis (OA) and rheumatoid arthritis (RA) are often difficult to distinguish in the early stage of the disease. The purpose of this study was to explore the similarities and differences between the two diseases through Mendelian randomization (MR) and transcriptome analysis.

Methods: We first performed a correlation analysis of phenotypic data from genome-wide association studies (GWAS) of OA and RA. Then, we performed functional and pathway enrichment of differentially expressed genes in OA, RA, and normal patients. The infiltration of immune cells in arthritis was analyzed according to gene expression. Finally, MR analysis was performed with inflammatory cytokines and immune cells as exposures and arthritis as the outcome. The same and different key cytokines and immune cells were obtained by the two analysis methods.

Results: GWAS indicated that there was a genetic correlation between OA and RA. The common function of OA and RA is enriched in their response to cytokines, while the difference is enriched in lymphocyte activation. T cells are the main immune cells that differentiate between OA and RA. MR analysis further revealed that OA is associated with more protective cytokines, and most of the cytokines in RA are pathogenic. In addition, CCR7 on naive CD4 + T cell was positively correlated with OA. SSC-A on CD4 + T cell was negatively correlated with RA, while HLA DR on CD33- HLA DR + was positively correlated with RA.

Conclusion: Our study demonstrated the similarities and differences of immune inflammation between OA and RA, allowing us to better understand these two diseases.

Keywords: Immune cells; Inflammatory cytokines; Mendelian randomization; Osteoarthritis (OA); Rheumatoid arthritis (RA).

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no conflicts of interest.

Figures

Fig. 1
Fig. 1
Genetic correlation of OA and RA. (A) Manhattan plot of OA specific 162 SNP loci. (B) Manhattan plot of RA specific 273 SNP loci. (C) Genetic correlation analysis of OA and RA after Bonferroni correction. (D) Overlapping genes between OA and RA
Fig. 2
Fig. 2
Differentially expressed genes identification. (A) Volcano map of DEGs between OA and normal controls. (B) Heatmap of top 50 DEGs between OA and normal control. (C) Volcano map of DEGs between RA and normal controls. (D) Heatmap of top 50 DEGs between RA and normal control. (E) Volcano map of DEGs between RA and OA. (F) Heatmap of top 50 DEGs between RA and OA
Fig. 3
Fig. 3
Enrichment analysis between RA and OA. (A) PCA clustering analysis of OA, RA and normal control samples. (B) Venn diagram screening for DEGs that are the common or different between OA and RA. (C) GO functional enrichment analysis of common DEGs between OA and RA. (D) KEGG pathway of analysis of common DEGs between OA and RA. (E) GO functional enrichment analysis of differential DEGs between OA and RA. (F) KEGG pathway of analysis of differential DEGs between OA and RA
Fig. 4
Fig. 4
Evaluation of immune cells obtained from transcriptome data using different algorithms. (A) The number of immune cells in OA, RA and normal control group obtained by the MCP algorithm. (B) The number of immune cells in OA, RA and normal control group obtained by the CIBERSORT algorithm
Fig. 5
Fig. 5
Using MR analysis to screen for inflammatory cytokines that have a statistically causal relationship with OA. (A-C) Forest plot of the causal relationships between total OA, knee OA, hip OA and significant inflammatory cytokines (OR < 1 indicates protection, OR > 1 indicates pathogenicity). (D-F) Circular map of causal relationships between total OA, knee OA, hip OA and all inflammatory cytokines (Red represents statistically significant)
Fig. 6
Fig. 6
Using MR analysis to screen for inflammatory cytokines that have a statistically causal relationship with RA. (A-C) Forest plot of the causal relationships between total RA, serum positive RA, serum negative RA and significant inflammatory cytokines (OR < 1 indicates protection, OR > 1 indicates pathogenicity). (D-F) Circular map of causal relationships between total RA, serum positive RA, serum negative RA and all inflammatory cytokines (Red represents statistically significant)
Fig. 7
Fig. 7
Using MR analysis to screen for immune cells that have a statistically causal relationship with OA. (A-C) Forest plot of the causal relationships between total OA, knee OA, hip OA and significant immune cells
Fig. 8
Fig. 8
Using MR analysis to screen for immune cells that have a statistically causal relationship with RA. (A-C) Forest plot of the causal relationships between total RA, serum positive RA, serum negative RA and significant immune cells
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Gessl I, et al. Role of joint damage, malalignment and inflammation in articular tenderness in rheumatoid arthritis, psoriatic arthritis and osteoarthritis. Ann Rheum Dis. 2021;80:884–90. 10.1136/annrheumdis-2020-218744. - PubMed
    1. Goldring MB, Goldring SR. Articular cartilage and subchondral bone in the pathogenesis of osteoarthritis. Ann N Y Acad Sci. 2010;1192:230–7. 10.1111/j.1749-6632.2009.05240.x. - PubMed
    1. Berenbaum F. Osteoarthritis as an inflammatory disease (osteoarthritis is not osteoarthrosis!). Osteoarthritis Cartilage. 2013;21:16–21. 10.1016/j.joca.2012.11.012. - PubMed
    1. de Lange-Brokaar BJ, et al. Synovial inflammation, immune cells and their cytokines in osteoarthritis: a review. Osteoarthritis Cartilage. 2012;20:1484–99. 10.1016/j.joca.2012.08.027. - PubMed
    1. Attur M, et al. Increased interleukin-1beta gene expression in peripheral blood leukocytes is associated with increased pain and predicts risk for progression of symptomatic knee osteoarthritis. Arthritis Rheum. 2011;63:1908–17. 10.1002/art.30360. - PMC - PubMed

Publication types

MeSH terms