Department of Internal Medicine III, Division of Rheumatology, Medical University of Vienna, Vienna, Wien, Austria
Arthrogen BV, Amsterdam, The Netherlands.
Ann Rheum Dis. 2021 Jun;80(6):714-726. doi: 10.1136/annrheumdis-2020-219247. Epub 2021 Feb 18.
Animal models for inflammatory arthritides such as rheumatoid arthritis (RA) and psoriatic arthritis are widely accepted and frequently used to identify pathological mechanisms and validate novel therapeutic strategies. Unfortunately, many publications reporting on these animal studies lack detailed description and appropriate assessment of the distinct histopathological features of arthritis: joint inflammation, cartilage damage and bone erosion. Therefore, the European consortium BeTheCure, consisting of 38 academic and industrial partners from 15 countries, set as goal to standardise the histological evaluation of joint sections from animal models of inflammatory arthritis. The consensual approach of a task force including 16 academic and industrial scientists as well as laboratory technicians has resulted in the development of the Standardised Microscopic Arthritis Scoring of Histological sections ('SMASH') recommendations for a standardised processing and microscopic scoring of the characteristic histopathological features of arthritis, exemplified by four different rodent models for arthritis: murine collagen-induced arthritis, collagen-antibody-induced arthritis, human tumour necrosis factor transgenic Tg197 mice and rat pristane-induced arthritis, applicable to any other inflammatory arthritis model. Through standardisation, the SMASH recommendations are designed to improve and maximise the information derived from in vivo arthritis experiments and to promote reproducibility and transparent reporting on such studies. In this manuscript, we will discuss and provide recommendations for analysis of histological joint sections: identification of the regions of interest, sample preparation, staining procedures and quantitative scoring methods. In conclusion, awareness of the different features of the arthritis pathology in animal models of inflammatory arthritis is of utmost importance for reliable research outcome, and the standardised histological processing and scoring methods in these SMASH recommendations will help increase uniformity and reproducibility in preclinical research on inflammatory arthritis.
用于炎症性关节炎(如类风湿关节炎和银屑病关节炎)的动物模型被广泛接受并经常用于鉴定病理机制和验证新的治疗策略。不幸的是,许多报道这些动物研究的出版物缺乏对关节炎的不同组织病理学特征的详细描述和适当评估:关节炎症、软骨损伤和骨侵蚀。因此,由来自 15 个国家的 38 个学术和工业合作伙伴组成的欧洲联盟 BeTheCure 将标准化炎症性关节炎动物模型关节切片的组织学评估作为目标。一个由 16 名学术和工业科学家以及实验室技术人员组成的工作组的共识方法促成了标准化微观关节炎评分组织学切片(“SMASH”)建议的制定,该建议用于标准化处理和关节炎的特征组织病理学特征的微观评分,以四种不同的关节炎啮齿动物模型为例:鼠胶原诱导关节炎、胶原抗体诱导关节炎、人肿瘤坏死因子转基因 Tg197 小鼠和大鼠 pristane 诱导关节炎,适用于任何其他炎症性关节炎模型。通过标准化,SMASH 建议旨在提高和最大限度地利用体内关节炎实验获得的信息,并促进此类研究的可重复性和透明报告。在本文中,我们将讨论并提供分析组织学关节切片的建议:确定感兴趣的区域、样品制备、染色程序和定量评分方法。总之,了解炎症性关节炎动物模型中关节炎病理学的不同特征对于可靠的研究结果至关重要,这些 SMASH 建议中的标准化组织学处理和评分方法将有助于提高炎症性关节炎临床前研究的一致性和可重复性。