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Updated: Oct 7, 2025
An Adoptive Transfer Model of Rheumatoid Arthritis in Mice
Published on: June 6, 2025
Central Role of Semaphorin 3B in a Serum-Induced Arthritis Model and Reduced Levels in Patients With Rheumatoid
Ana Igea1, Tiago Carvalheiro2, Beatriz Malvar-Fernández3
1Universidade de Vigo, Campus Universitario Lagoas Marcosende, and Galicia Sur Health Research Institute, Servicio Galego de Saúde Universidade de Vigo, Vigo, Spain.
Objective:
Semaphorin 3B (Sema3B) decreases the migratory and invasive capacities of fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA) and suppresses expression of matrix metalloproteinases. We undertook this study to examine the role of Sema3B in a mouse model of arthritis and its expression in RA patients.
Methods:
Clinical responses, histologic features, and FLS function were examined in wild-type (WT) and Sema3B-/- mice in a K/BxN serum transfer model of arthritis. Protein and messenger RNA expression of Sema3B in mouse joints and murine FLS, as well as in serum and synovial tissue from patients with arthralgia and patients with RA, was determined using enzyme-linked immunosorbent assay, immunoblotting, quantitative polymerase chain reaction, and RNA sequencing. FLS migration was determined using a wound closure assay.
Results:
The clinical severity of serum-induced arthritis was significantly higher in Sema3B-/- mice compared to WT mice. This was associated with increased expression of inflammatory mediators and increased migratory capacity of murine FLS. Administration of recombinant mouse Sema3B reduced the clinical severity of serum-induced arthritis and the expression of inflammatory mediators. Sema3B expression was significantly lower in the synovial tissue and serum of patients with established RA compared to patients with arthralgia. Serum Sema3B levels were elevated in patients with arthralgia that later progressed to RA, but not in those who did not develop RA; however, these levels drastically decreased 1 and 2 years after RA development.
Conclusion:
Sema3B expression plays a protective role in a mouse model of arthritis. In RA patients, expression levels of Sema3B in the serum depend on the disease stage, suggesting different regulatory roles in disease onset and progression.
Insights
Semaphorin 3B (Sema3B) has a protective role in arthritis, reducing inflammation and cell migration. In rheumatoid arthritis (RA) patients, Sema3B levels vary with disease stage, impacting onset and progression.
Area of Science:
- Immunology
- Rheumatology
- Molecular Biology
Background:
- Fibroblast-like synoviocytes (FLS) play a key role in rheumatoid arthritis (RA) pathogenesis.
- Semaphorin 3B (Sema3B) is known to inhibit FLS migration and matrix metalloproteinase expression.
- The specific role of Sema3B in arthritis development and RA progression requires further investigation.
Purpose of the Study:
- To investigate the therapeutic potential of Sema3B in a mouse model of arthritis.
- To analyze the expression patterns of Sema3B in relation to arthritis severity and RA progression in patients.
Main Methods:
- Utilized a K/BxN serum transfer-induced arthritis model in wild-type (WT) and Sema3B knockout (Sema3B-/-) mice.
- Assessed clinical and histological features, FLS migratory capacity, and inflammatory mediator expression.
- Quantified Sema3B protein and mRNA levels in murine tissues and FLS, as well as in serum and synovial tissue from human patients with arthralgia and RA using ELISA, immunoblotting, qPCR, and RNA sequencing.
Main Results:
- Sema3B-/- mice exhibited exacerbated arthritis severity, increased inflammation, and enhanced FLS migration compared to WT mice.
- Recombinant Sema3B administration attenuated arthritis symptoms and reduced inflammatory markers in mice.
- RA patients displayed significantly lower Sema3B expression in synovial tissue and serum compared to arthralgia patients.
- Elevated serum Sema3B in arthralgia patients predicted RA development, with levels decreasing post-RA diagnosis.
Conclusions:
- Sema3B demonstrates a protective role in arthritis, mitigating disease severity and FLS hypermotility.
- Sema3B serum levels in RA patients are dynamic, correlating with disease stage and potentially influencing disease onset and progression.
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