BACKGROUND Notch pathway is highly conserved across species and is involved in the regulation of cell differentiation and activity both in embryonic development and adult life. Notch signaling has an important role in the development of hematopoietic stem cells and their differentiation to committed lineages, as well as in the regulation of several non-hematopoietic cell lines. OBJECTIVE As Notch signaling has been implicated in various inflammatory and autoimmune diseases, it is of interest to elucidate what role do Notch receptors and ligands have in inflammatory arthritides. METHODS We performed a search on the role of Notch receptors (1-4) and Notch ligands Delta-like (DLL) 1, 3, 4 and Jagged (Jag) 1 and 2 in animal models of inflammatory arthritis and most common types of human inflammatory arthritis (rheumatoid arthritis, psoriatic arthritis or ankylosing spondylitis). The initial search identified 135 unique articles, of which 24 were ultimately deemed relevant and included in this systematic review. RESULTS Overall, identified articles describe roles for Notch ligands and receptors in inflammatory arthritis, with Notch activation resulting in enhanced Th1/17 polarization, osteoclast differentiation, macrophage activation and fibroblast-like synoviocyte proliferation. However, the inhibitory role of Notch signaling, especially by Jag1 is also described. CONCLUSION There is evidence that Notch pathway activation affects multiple cell lineages present within the arthritic environment, therefore potentially acting as one of the drivers of disease pathogenesis. Since cell lineage-selective transgenic mouse models and specific Notch receptor inhibitors are becoming increasingly available, it can be expected that future research will evaluate whether Notch signaling components initiate crucial pathogenic impulses and, therefore, present viable therapeutic targets in inflammatory arthritis.

中文翻译：

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炎性关节炎中的Notch受体和配体-系统评价。

背景技术Notch途径在整个物种中是高度保守的，并且参与胚胎发育和成年生活中细胞分化和活性的调节。Notch信号在造血干细胞的发育及其向定型谱系的分化以及几种非造血细胞系的调节中具有重要作用。目的由于Notch信号传导已牵涉到各种炎性和自身免疫性疾病中，阐明Notch受体和配体在炎性关节炎中的作用是有意义的。方法我们研究了Notch受体（1-4）和Notch配体Delta-like（DLL）1、3、4和Jagged（Jag）1和2在炎症性关节炎和大多数人类常见​​动物模型中的作用炎性关节炎（类风湿关节炎，银屑病关节炎或强直性脊柱炎）。初步搜索确定了135篇独特的文章，其中24篇最终被认为是相关的，并包含在本系统综述中。结果总体而言，已鉴定的文章描述了Notch配体和受体在炎性关节炎中的作用，Notch激活导致增强的Th1 / 17极化，破骨细胞分化，巨噬细胞激活和成纤维细胞样滑膜细胞增殖。但是，还描述了Notch信号的抑制作用，尤其是Jag1的抑制作用。结论有证据表明，Notch途径的活化会影响关节炎环境中存在的多种细胞谱系，因此可能是疾病发病机理的驱动因素之一。