ArticleArthritis research & therapy2025
Semaphorin4B is elevated in rheumatoid arthritis and enhances the inflammatory phenotype of macrophages and fibroblast-like synoviocytes.
Article in Arthritis research & therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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3 citing papers in PubMed.
- Structural diversity of lipid A modulates neutrophil proteome and secretome responses.Journal of proteomics · 2026Article
- Hyaluronic acid microneedle patch for transdermal delivery of naringin-loaded PEGylated terpesomes in a rat model of rheumatoid arthritis: Modulation TGF-β1, oxidative stress, and inflammation.International journal of pharmaceutics: X · 2026Article
- SEMA4A signaling in macrophage subpopulations and its implication in osteoarthritis.Frontiers in immunology · 2026Article
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17 authors.
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Abstract
backgroundSeveral members of the class 4 semaphorins are involved in the pathogenesis of rheumatoid arthritis (RA), regulating proinflammatory functions, but the role of (Sema)phorin4B remains unexplored. Therefore, the aim of this study was to determine the expression and function of Sema4B in RA.
methodsPeripheral blood monocytes from healthy controls (HC) and patients with RA were differentiated into M1 macrophages and stimulated with Sema4B and LPS alone and in combination. Fibroblast-like synoviocytes (FLS) from patients with osteoarthritis (OA) and RA and 3D synovium micromasses, formed by RA FLS and RA monocytes, were stimulated with Sema4B and TNF-α alone and in combination. PlexinB2 expression was knocked down using siRNA. Synovial mRNA expression was obtained from gene expression array in GEO-NCBI and determined by (q)uantitative PCR. Protein expression was determined by immunohistochemistry, immunoblotting and ELISA. FLS viability, invasion and migration were determined using calcein, invasion and wound repair scratch assays, respectively.
resultsThe expression of Sema4B was higher in the synovial tissue of patients with RA, as well as in RA FLS compared to OA FLS. Importantly, the stimulation of RA FLS and RA MØ with inflammatory mediators induced the expression of Sema4B. Functionally, Sema4B alone induced FLS migration and invasion, and enhanced the TNF-α or LPS-induced production of inflammatory mediators (Interleukin (IL)-6, IL-8, TNF-α, CCL-2) and matrix metalloproteases (MMP-1 and MMP-3) in RA FLS, RA MØ and the 3D synovium model. In RA FLS, this effect was mediated by the receptor PlexinB2.
conclusionsIn an inflammatory context, Sema4B induces an aggressive FLS phenotype and the production of pro-inflammatory mediators by FLS and MØ. These results suggest that Sema4B is involved in the pathogenic processes observed within the RA synovium.
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