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Updated: Jan 5, 2026

An Adoptive Transfer Model of Rheumatoid Arthritis in Mice
Published on: June 6, 2025
MicroRNA-421 promotes inflammatory response of fibroblast-like synoviocytes in rheumatoid arthritis by targeting
1Department of General Medicine, Beijing Luhe Hospital, Capital Medical University, Beijing, China. 1034556389@qq.com.
Objective:
The aim of this study was to investigate whether microRNA-421 could participate in the proliferative, migratory and inflammatory changes of fibroblast-like synoviocytes (FLS) in rheumatoid arthritis by targeting SPRY1.
Patients And Methods:
The expressions of microRNA-421 and SPRY1 in synovial tissues and FLS were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Western blot, respectively. The binding condition between microRNA-421 and SPRY1 was verified by the Dual-Luciferase reporter gene assay. MicroRNA-421 mimics and inhibitor were constructed and transfected. The levels of extracellular interleukin-1 (IL-1), IL-6, and COX2 in FLS after microRNA-421 mimics or inhibitor transfection were detected by enzyme-linked immunosorbent assay (ELISA). The regulatory effect of microRNA-421 on the proliferation and migration of FLS was detected using cell counting kit-8 (CCK-8) and transwell assay, respectively. Furthermore, collagen-induced RA mouse model was constructed to confirm the specific effect of microRNA-421 on regulating RA development.
Results:
MicroRNA-421 was highly expressed in the synovial tissues of RA patients. SPRY1 expression in FLS was negatively regulated by microRNA-421. Moreover, the overexpression of microRNA-421 significantly promoted proliferative, invasive potentials and inflammatory response of FLS. In vivo, RA mouse model indicated that downregulated microRNA-421 and upregulated SPRY1 were observed in mice injected with cortisone and microRNA-421 inhibitor when compared with those of controls.
Conclusions:
MicroRNA-421 promotes the inflammatory response of fibroblast-like synoviocytes in rheumatoid arthritis by downregulating the SPRY1 expression.
Insights
MicroRNA-421 promotes rheumatoid arthritis by increasing fibroblast-like synoviocyte activity and inflammation through SPRY1 downregulation. This study reveals a key mechanism in RA pathogenesis.
Area of Science:
- Molecular Biology
- Immunology
- Rheumatology
Background:
- Rheumatoid arthritis (RA) is characterized by fibroblast-like synoviocyte (FLS) proliferation, migration, and inflammation.
- The role of microRNAs in RA pathogenesis is an area of active investigation.
Purpose of the Study:
- To investigate the role of microRNA-421 (miR-421) in regulating FLS behavior in RA.
- To determine if miR-421 targets SPRY1 to influence FLS proliferation, migration, and inflammation.
Main Methods:
- Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Western blot to assess miR-421 and SPRY1 expression.
- Dual-Luciferase reporter assay to confirm miR-421 binding to SPRY1.
- In vitro assays (CCK-8, transwell, ELISA) and an in vivo collagen-induced RA mouse model to evaluate FLS function and RA development.
Main Results:
- miR-421 was highly expressed in RA synovial tissues and FLS.
- miR-421 negatively regulated SPRY1 expression.
- Overexpression of miR-421 promoted FLS proliferation, migration, and inflammatory response.
- In vivo, reduced miR-421 and increased SPRY1 were observed in RA mice treated with cortisone and miR-421 inhibitor.
Conclusions:
- miR-421 promotes FLS-driven inflammation in rheumatoid arthritis.
- This effect is mediated by the downregulation of SPRY1 expression.
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