The inhibitory effect of tocilizumab on systemic bone loss and tendon inflammation in a juvenile Collagen-Induced arthritis rat model.

IF 2.8 4区医学 Q3 CELL BIOLOGY

Connective Tissue Research Pub Date : 2022-11-01 Epub Date: 2022-02-17 DOI:10.1080/03008207.2022.2042275

Frideriki Poutoglidou, Chryssa Pourzitaki, Maria Eleni Manthou, Efthimios Samoladas, Athanasios Saitis, Foteini Malliou, Dimitrios Kouvelas

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引用次数: 1

Abstract

Purpose of the study: Reduced Bone Mineral Density (BMD) is a prevalent comorbidity in Juvenile Idiopathic Arthritis (JIA). Enthesitis and other tendon abnormalities, such as tenosynovitis, tendinitis and tendon ruptures are, also, common extra-articular manifestations of the disease. The aim of the present study was to investigate the effect of tocilizumab, an antibody that binds the Interleukin-6 (IL-6) Receptor, on inflammation-related bone loss and tendon inflammation in an animal model of JIA.

Materials and methods: The Collagen-Induced Arthritis (CIA) model was induced in male rats followed by intraperitoneal administration of tocilizumab for 8 weeks. Methotrexate, the most widely used Disease-Modifying Antirheumatic Drug in the management of JIA, was, also, administered, either as a monotherapy or as an add-on therapy to tocilizumab. BMD was evaluated with Micro-Computed Tomography (Micro-CT) and histopathological examination. Tendon damage was, also, assessed histologically. Finally, two pro-inflammatory cytokines, Tumor Necrosis Factor-alpha (TNF-a) and Interleukin-23 (IL-23) were quantified in tendon tissues by ELISA analysis.

Results: Tocilizumab-treated animals exhibited a significantly improved trabecular microarchitecture on micro-CT analysis and histological examination. Tendon morphology was also improved. Anti-IL-6 treatment led to a significant decrease in TNF-a and IL-23 expression in tendon tissue.

Conclusions: The results of the present study provide evidence that tocilizumab reduces inflammation-related bone loss and suppresses tendon inflammation in a juvenile CIA rat model. These findings offer perspectives for the management of osteoporosis and enthesitis in JIA.

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托珠单抗在幼年胶原诱导关节炎大鼠模型中对全身骨质流失和肌腱炎症的抑制作用。

研究目的:骨密度降低(BMD)是青少年特发性关节炎(JIA)的常见合并症。腱鞘炎和其他肌腱异常，如腱鞘炎、肌腱炎和肌腱断裂，也是本病常见的关节外表现。本研究的目的是研究tocilizumab(一种结合白细胞介素-6 (IL-6)受体的抗体)在JIA动物模型中对炎症相关性骨质流失和肌腱炎症的影响。材料与方法:建立雄性大鼠胶原诱导关节炎(CIA)模型，并腹腔注射托珠单抗8周。甲氨蝶呤是JIA治疗中最广泛使用的改善疾病的抗风湿药物，也可以作为单药治疗或作为托珠单抗的附加治疗。采用显微计算机断层扫描(Micro-CT)和组织病理学检查评估骨密度。肌腱损伤也进行了组织学评估。最后，采用ELISA法测定肌腱组织中两种促炎因子肿瘤坏死因子- α (TNF-a)和白细胞介素-23 (IL-23)的含量。结果:tocilizumab治疗的动物在显微ct分析和组织学检查中表现出明显改善的小梁微结构。肌腱形态也得到改善。抗il -6治疗可显著降低肌腱组织中TNF-a和IL-23的表达。结论:本研究的结果提供了证据，证明tocilizumab可以减少炎症相关的骨质流失，并抑制幼年CIA大鼠模型中的肌腱炎症。这些发现为JIA的骨质疏松症和胃炎的治疗提供了新的视角。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Connective Tissue Research 生物-细胞生物学

CiteScore

6.60

自引率

3.40%

发文量

审稿时长

2 months

期刊介绍： The aim of Connective Tissue Research is to present original and significant research in all basic areas of connective tissue and matrix biology. The journal also provides topical reviews and, on occasion, the proceedings of conferences in areas of special interest at which original work is presented. The journal supports an interdisciplinary approach; we present a variety of perspectives from different disciplines, including Biochemistry Cell and Molecular Biology Immunology Structural Biology Biophysics Biomechanics Regenerative Medicine The interests of the Editorial Board are to understand, mechanistically, the structure-function relationships in connective tissue extracellular matrix, and its associated cells, through interpretation of sophisticated experimentation using state-of-the-art technologies that include molecular genetics, imaging, immunology, biomechanics and tissue engineering.