TY - JOUR
T1 - Central Role of Semaphorin 3B in a Serum-Induced Arthritis Model and Reduced Levels in Patients With Rheumatoid Arthritis
AU - Igea, Ana
AU - Carvalheiro, Tiago
AU - Malvar-Fernández, Beatriz
AU - Martinez-Ramos, Sara
AU - Rafael-Vidal, Carlos
AU - Niemantsverdriet, Ellis
AU - Varadé, Jezabel
AU - Fernández-Carrera, Andrea
AU - Jimenez, Norman
AU - McGarry, Trudy
AU - Rodriguez-Trillo, Angela
AU - Veale, Douglas
AU - Fearon, Ursula
AU - Conde, Carmen
AU - Pego-Reigosa, Jose M
AU - González-Fernández, África
AU - Reedquist, Kris A
AU - Radstake, Timothy R D J
AU - van der Helm-Van Mil, Annette
AU - García, Samuel
N1 - © 2022 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.
PY - 2022/6
Y1 - 2022/6
N2 - 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.
AB - 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.
KW - Animals
KW - Arthralgia/genetics
KW - Arthritis, Rheumatoid/genetics
KW - Cells, Cultured
KW - Fibroblasts/metabolism
KW - Humans
KW - Inflammation Mediators/metabolism
KW - Membrane Glycoproteins/genetics
KW - Mice
KW - Semaphorins/genetics
KW - Synovial Membrane/metabolism
KW - Synoviocytes/metabolism
U2 - 10.1002/art.42065
DO - 10.1002/art.42065
M3 - Article
C2 - 35001548
SN - 2326-5191
VL - 74
SP - 972
EP - 983
JO - Arthritis & rheumatology (Hoboken, N.J.)
JF - Arthritis & rheumatology (Hoboken, N.J.)
IS - 6
ER -