Universidade de Vigo, Campus Universitario Lagoas Marcosende, and Galicia Sur Health Research Institute, Servicio Galego de Saúde Universidade de Vigo, Vigo, Spain.
University of Utrecht, Utrecht, The Netherlands.
Arthritis Rheumatol. 2022 Jun;74(6):972-983. doi: 10.1002/art.42065. Epub 2022 Apr 13.
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.
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.
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.
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.
信号素 3B（Sema3B）可降低类风湿关节炎（RA）成纤维样滑膜细胞（FLS）的迁移和侵袭能力，并抑制基质金属蛋白酶的表达。我们进行这项研究旨在探讨 Sema3B 在关节炎小鼠模型中的作用及其在 RA 患者中的表达。
在 K/BxN 血清转移关节炎模型中，观察野生型（WT）和 Sema3B 小鼠的临床反应、组织学特征和 FLS 功能。采用酶联免疫吸附试验、免疫印迹、实时定量聚合酶链反应和 RNA 测序检测 Sema3B 在小鼠关节和鼠 FLS 中的蛋白和信使 RNA 表达，以及在关节痛患者和 RA 患者血清和滑膜组织中的表达。采用划痕实验检测 FLS 迁移。
与 WT 小鼠相比，Sema3B 小鼠血清诱导关节炎的临床严重程度显著升高。这与炎症介质表达增加和鼠 FLS 迁移能力增强有关。给予重组鼠 Sema3B 可降低血清诱导关节炎的临床严重程度和炎症介质的表达。与关节痛患者相比，已确诊 RA 患者的滑膜组织和血清中的 Sema3B 表达明显降低。在关节痛患者中，以后进展为 RA 的患者血清 Sema3B 水平升高，但未进展为 RA 的患者血清 Sema3B 水平不升高；然而，这些水平在 RA 发病后 1 年和 2 年急剧下降。
Sema3B 表达在关节炎小鼠模型中发挥保护作用。在 RA 患者中，血清中 Sema3B 的表达水平取决于疾病阶段，提示其在疾病发病和进展中具有不同的调节作用。
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