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

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 exp...

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Autores principales: Igea, Ana, Carvalheiro, Tiago, Malvar‐Fernández, Beatriz, Martinez‐Ramos, Sara, Rafael‐Vidal, Carlos, Niemantsverdriet, Ellis, Varadé, Jezabel, Fernández‐Carrera, Andrea, Jimenez, Norman, McGarry, Trudy, Rodriguez‐Trillo, Angela, Veale, Douglas, Fearon, Ursula, Conde, Carmen, Pego‐Reigosa, Jose M., González‐Fernández, África, Reedquist, Kris A., Radstake, Timothy R. D. J., van der Helm‐Van Mil, Annette, García, Samuel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Wiley Periodicals, Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9322571/
https://www.ncbi.nlm.nih.gov/pubmed/35001548
http://dx.doi.org/10.1002/art.42065
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author Igea, Ana
Carvalheiro, Tiago
Malvar‐Fernández, Beatriz
Martinez‐Ramos, Sara
Rafael‐Vidal, Carlos
Niemantsverdriet, Ellis
Varadé, Jezabel
Fernández‐Carrera, Andrea
Jimenez, Norman
McGarry, Trudy
Rodriguez‐Trillo, Angela
Veale, Douglas
Fearon, Ursula
Conde, Carmen
Pego‐Reigosa, Jose M.
González‐Fernández, África
Reedquist, Kris A.
Radstake, Timothy R. D. J.
van der Helm‐Van Mil, Annette
García, Samuel
author_facet Igea, Ana
Carvalheiro, Tiago
Malvar‐Fernández, Beatriz
Martinez‐Ramos, Sara
Rafael‐Vidal, Carlos
Niemantsverdriet, Ellis
Varadé, Jezabel
Fernández‐Carrera, Andrea
Jimenez, Norman
McGarry, Trudy
Rodriguez‐Trillo, Angela
Veale, Douglas
Fearon, Ursula
Conde, Carmen
Pego‐Reigosa, Jose M.
González‐Fernández, África
Reedquist, Kris A.
Radstake, Timothy R. D. J.
van der Helm‐Van Mil, Annette
García, Samuel
author_sort Igea, Ana
collection PubMed
description 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.
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spelling pubmed-93225712022-07-30 Central Role of Semaphorin 3B in a Serum‐Induced Arthritis Model and Reduced Levels in Patients With Rheumatoid Arthritis Igea, Ana Carvalheiro, Tiago Malvar‐Fernández, Beatriz Martinez‐Ramos, Sara Rafael‐Vidal, Carlos Niemantsverdriet, Ellis Varadé, Jezabel Fernández‐Carrera, Andrea Jimenez, Norman McGarry, Trudy Rodriguez‐Trillo, Angela Veale, Douglas Fearon, Ursula Conde, Carmen Pego‐Reigosa, Jose M. González‐Fernández, África Reedquist, Kris A. Radstake, Timothy R. D. J. van der Helm‐Van Mil, Annette García, Samuel Arthritis Rheumatol Rheumatoid Arthritis 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. Wiley Periodicals, Inc. 2022-04-13 2022-06 /pmc/articles/PMC9322571/ /pubmed/35001548 http://dx.doi.org/10.1002/art.42065 Text en © 2022 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Rheumatoid Arthritis
Igea, Ana
Carvalheiro, Tiago
Malvar‐Fernández, Beatriz
Martinez‐Ramos, Sara
Rafael‐Vidal, Carlos
Niemantsverdriet, Ellis
Varadé, Jezabel
Fernández‐Carrera, Andrea
Jimenez, Norman
McGarry, Trudy
Rodriguez‐Trillo, Angela
Veale, Douglas
Fearon, Ursula
Conde, Carmen
Pego‐Reigosa, Jose M.
González‐Fernández, África
Reedquist, Kris A.
Radstake, Timothy R. D. J.
van der Helm‐Van Mil, Annette
García, Samuel
Central Role of Semaphorin 3B in a Serum‐Induced Arthritis Model and Reduced Levels in Patients With Rheumatoid Arthritis
title Central Role of Semaphorin 3B in a Serum‐Induced Arthritis Model and Reduced Levels in Patients With Rheumatoid Arthritis
title_full Central Role of Semaphorin 3B in a Serum‐Induced Arthritis Model and Reduced Levels in Patients With Rheumatoid Arthritis
title_fullStr Central Role of Semaphorin 3B in a Serum‐Induced Arthritis Model and Reduced Levels in Patients With Rheumatoid Arthritis
title_full_unstemmed Central Role of Semaphorin 3B in a Serum‐Induced Arthritis Model and Reduced Levels in Patients With Rheumatoid Arthritis
title_short Central Role of Semaphorin 3B in a Serum‐Induced Arthritis Model and Reduced Levels in Patients With Rheumatoid Arthritis
title_sort central role of semaphorin 3b in a serum‐induced arthritis model and reduced levels in patients with rheumatoid arthritis
topic Rheumatoid Arthritis
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9322571/
https://www.ncbi.nlm.nih.gov/pubmed/35001548
http://dx.doi.org/10.1002/art.42065
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