Bench to Bedside: Modelling Inflammatory Arthritis.

Discovery immunology Pub Date : 2022-11-23 eCollection Date: 2023-01-01 DOI:10.1093/discim/kyac010
Chiamaka I Chidomere, Mussarat Wahid, Samuel Kemble, Caroline Chadwick, Richard Thomas, Rowan S Hardy, Helen M McGettrick, Amy J Naylor
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Abstract

Inflammatory arthritides such as rheumatoid arthritis are a major cause of disability. Pre-clinical murine models of inflammatory arthritis continue to be invaluable tools with which to identify and validate therapeutic targets and compounds. The models used are well-characterised and, whilst none truly recapitulates the human disease, they are crucial to researchers seeking to identify novel therapeutic targets and to test efficacy during preclinical trials of novel drug candidates. The arthritis parameters recorded during clinical trials and routine clinical patient care have been carefully standardised, allowing comparison between centres, trials, and treatments. Similar standardisation of scoring across in vivo models has not occurred, which makes interpretation of published results, and comparison between arthritis models, challenging. Here, we include a detailed and readily implementable arthritis scoring system, that increases the breadth of arthritis characteristics captured during experimental arthritis and supports responsive and adaptive monitoring of disease progression in murine models of inflammatory arthritis. In addition, we reference the wider ethical and experimental factors researchers should consider during the experimental design phase, with emphasis on the continued importance of replacement, reduction, and refinement of animal usage in arthritis research.

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长凳到床边:炎症性关节炎建模
炎症性关节炎,如风湿性关节炎是致残的主要原因。炎症性关节炎的临床前小鼠模型仍然是识别和验证治疗靶点和化合物的宝贵工具。所使用的模型具有良好的特征,虽然没有一个真正概括人类疾病,但它们对寻求确定新的治疗靶点和在新的候选药物的临床前试验中测试功效的研究人员至关重要。在临床试验和常规临床患者护理期间记录的关节炎参数已被仔细标准化,允许在中心,试验和治疗之间进行比较。在体内模型中类似的评分标准化尚未发生,这使得对已发表的结果的解释和关节炎模型之间的比较具有挑战性。在这里,我们包括一个详细且易于实施的关节炎评分系统,该系统增加了实验性关节炎期间捕获的关节炎特征的广度,并支持炎症性关节炎小鼠模型中疾病进展的反应性和适应性监测。此外,我们参考了研究人员在实验设计阶段应考虑的更广泛的伦理和实验因素,重点是关节炎研究中动物使用的替代、减少和改进的持续重要性。
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