Role of Semaphorins in Immunopathologies and Rheumatic Diseases

García, Samuel

doi:10.3390/ijms20020374

Cited by 34 publications

(24 citation statements)

References 85 publications

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“…Next, we investigated the possible molecular mechanisms involved in the elevated severity of arthritis in this murine model. First, we analyzed expression of the Sema3B receptors, the plexin A family members, and the coreceptors neuropilin 1 (NRP-1) and NRP-2 (5)(6)(7)19). We found that expression of Nrp1 and Plexina2 was significantly lower in the joints of arthritic Sema3B −/− mice compared to the joints of WT and Sema3B −/− nonarthritic mice.…”

Section: Resultsmentioning

confidence: 99%

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

Igea

Carvalheiro

Malvar‐Fernández

et al. 2022

Arthritis & Rheumatology

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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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Section: Resultsmentioning

confidence: 99%

“…Semaphorin 3B (Sema3B) is a secreted protein belonging to the semaphorin family involved in different biologic processes, such as apoptosis, angiogenesis, cell migration, and invasion (5)(6)(7). A recent study from our group implicated Sema3B in the pathogenesis of RA (8).…”

Section: Introductionmentioning

confidence: 99%

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

Igea

Carvalheiro

Malvar‐Fernández

et al. 2022

Arthritis & Rheumatology

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“…Sema3A becomes an immunosuppressive regulator that can initiate an immune inhibitory response by making a complex with neuropilin-1 and plexin-A4 [33]. This action was proven in several studies through the induction of Sema3A expression in animal models with arthritis and reported reduced severity and damage of articular surface [34].…”

Section: Discussionmentioning

confidence: 97%

Evaluation of serum14-3-3η protein and Sema3A levels in rheumatoid arthritis: diagnostic and prognostic value

Darwish

Hablas

Baiomy

et al. 2020

Egypt Rheumatol Rehabil

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Background Serum14-3-3η protein plays an important role in the pathogenesis of rheumatoid arthritis (RA) as it is a joint-derived proinflammatory mediator. Semaphorin3A (Sema3A) plays an immune regulatory and bone remodeling role in many autoimmune diseases. Their role in rheumatoid arthritis needs to be evaluated for diagnostic and prognostic prospective values. Results The serum level of protein 14-3-3n was significantly higher in patients with RA than those in healthy controls. Serum 14-3-3η has a significant positive correlation with RF and ACPA, but not with either DAS28, ESR, or CRP. Serum 14-3-3η levels were significantly correlated with radiographically assessed joint damage. Serum Sema3A levels were decreased in rheumatoid arthritis patients compared to controls. There were also negative correlations with disease duration and activity score (DAS28), ESR, CRP, and RF. Conclusion The discriminative ability of 14-3-3η was comparable to RF and ACPA enhancing its diagnostic capacity. Sema 3A might serve as a predictive marker for radiographic severity and could have a potential therapeutic role in RA.

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“… 51 Semaphorin 3D, encoded by SEMA3D , is a member of the semaphorin family of axon guidance factors involved in nervous system development. 52 Evidently, semaphorins, such as SEMA3A , may be a potential target in OA, although the detailed roles of this family remain to be elucidated.…”

Section: Discussionmentioning

confidence: 99%

Identification of mechanics-responsive osteocyte signature in osteoarthritis subchondral bone

Zhou

Cui

et al. 2022

Bone & Joint Research

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Aims Osteoarthritis (OA) is a common degenerative joint disease. The osteocyte transcriptome is highly relevant to osteocyte biology. This study aimed to explore the osteocyte transcriptome in subchondral bone affected by OA. Methods Gene expression profiles of OA subchondral bone were used to identify disease-relevant genes and signalling pathways. RNA-sequencing data of a bone loading model were used to identify the loading-responsive gene set. Weighted gene co-expression network analysis (WGCNA) was employed to develop the osteocyte mechanics-responsive gene signature. Results A group of 77 persistent genes that are highly relevant to extracellular matrix (ECM) biology and bone remodelling signalling were identified in OA subchondral lesions. A loading responsive gene set, including 446 principal genes, was highly enriched in OA medial tibial plateaus compared to lateral tibial plateaus. Of this gene set, a total of 223 genes were identified as the main contributors that were strongly associated with osteocyte functions and signalling pathways, such as ECM modelling, axon guidance, Hippo, Wnt, and transforming growth factor beta (TGF-β) signalling pathways. We limited the loading-responsive genes obtained via the osteocyte transcriptome signature to identify a subgroup of genes that are highly relevant to osteocytes, as the mechanics-responsive osteocyte signature in OA. Based on WGCNA, we found that this signature was highly co-expressed and identified three clusters, including early, late, and persistently responsive genes. Conclusion In this study, we identified the mechanics-responsive osteocyte signature in OA-lesioned subchondral bone. Cite this article: Bone Joint Res 2022;11(6):362–370.

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Role of Semaphorins in Immunopathologies and Rheumatic Diseases

Cited by 34 publications

References 85 publications

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

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

Evaluation of serum14-3-3η protein and Sema3A levels in rheumatoid arthritis: diagnostic and prognostic value

Identification of mechanics-responsive osteocyte signature in osteoarthritis subchondral bone

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