Central Role of Semaphorin 3B in a Serum-Induced Arthritis Model and Reduced Levels in Patients With Rheumatoid Arthritis

Ana Igea, Tiago Carvalheiro, Beatriz Malvar-Fernández, Sara Martinez-Ramos, Carlos Rafael-Vidal, Ellis Niemantsverdriet, Jezabel Varadé, Andrea Fernández-Carrera, Norman Jimenez, Trudy McGarry, Angela Rodriguez-Trillo, Douglas Veale, Ursula Fearon, Carmen Conde, Jose M Pego-Reigosa, África González-Fernández, Kris A Reedquist, Timothy R D J Radstake, Annette van der Helm-Van Mil, Samuel García

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

Samenvatting

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.

Originele taal-2Engels
Pagina's (van-tot)972-983
Aantal pagina's12
TijdschriftArthritis & rheumatology (Hoboken, N.J.)
Volume74
Nummer van het tijdschrift6
DOI's
StatusGepubliceerd - jun. 2022

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