CD73 blockade alleviates collagen-induced arthritis by inhibiting synovial fibroblast activity

Articles in Press

Document Type : Original Article

Authors

Department of Clinical Laboratory, Tangdu Hospital, Fourth Military Medical University, Xi’an, China

10.22038/ijbms.2026.86913.18777

Abstract

Objective(s): Rheumatoid arthritis (RA) is a chronic autoimmune disease with progressive cartilage erosion and joint destruction. CD73 plays a critical role in regulating inflammatory responses. This study aims to investigate the effects of CD73 blockade on RA progression and explore the potential mechanism.
Materials and Methods: Soluble CD73 levels were determined by enzyme-linked immunosorbent assay. Immunohistochemistry (IHC) was used to detect CD73 expression in tissues. A collagen-induced arthritis (CIA) rat model was used to evaluate the effect of CD73 inhibitors in vivo. Hematoxylin and eosin staining was used to evaluate synovial tissue inflammation. Safranin O/Fast Green staining and Micro-CT were used to evaluate cartilage erosion and bone destruction. A live cell imaging system was used to analyze cell proliferation. Cell invasion experiments were performed using Transwell chambers. 
Results: Our data showed that CD73 expression was significantly increased in synovial tissues and serum from RA patients. The increased CD73 expression may be attributed to the hypoxic microenvironment via the hypoxia-inducible factor pathway in synovial tissues. Using CIA rats, our data demonstrated that CD73 blockade alleviated bone destruction and synovial inflammation. CD73 blockade inhibited synovioblast proliferation, invasion, and pro-inflammatory cytokine production. Moreover, transcriptome analysis revealed that differentially expressed genes (DEGs) in synovioblasts induced by CD73 blockade were primarily enriched for inflammatory responses, neutrophil chemotaxis, and integrin-mediated signaling pathways.
Conclusion: CD73 blockade alleviated RA disease progression by regulating the activity of synovial fibroblasts. CD73 blockade is a potential therapeutic approach for patients with RA.

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References

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Iranian Journal of Basic Medical Sciences

Articles in Press, Accepted Manuscript
Available Online from 21 April 2026

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