Xu Luyang, Kazezian Zepur, Pitsillides Andrew A, Bull Anthony M J
Department of Bioengineering, Imperial College London, London, United Kingdom.
Centre for Blast Injury Studies, Imperial College London, London, United Kingdom.
Front Bioeng Biotechnol. 2024 Jul 25;12:1408015. doi: 10.3389/fbioe.2024.1408015. eCollection 2024.
Osteoarthritis (OA) is a common chronic disease largely driven by mechanical factors, causing significant health and economic burdens worldwide. Early detection is challenging, making animal models a key tool for studying its onset and mechanically-relevant pathogenesis. This review evaluate current use of preclinical models and progressive measurement techniques for analysing biomechanical factors in the specific context of the clinical OA phenotypes. It categorizes preclinical models into naturally occurring, genetically modified, chemically-induced, surgically-induced, and non-invasive types, linking each to clinical phenotypes like chronic pain, inflammation, and mechanical overload. Specifically, we discriminate between mechanical and biological factors, give a new explanation of the mechanical overload OA phenotype and propose that it should be further subcategorized into two subtypes, post-traumatic and chronic overloading OA. This review then summarises the representative models and tools in biomechanical studies of OA. We highlight and identify how to develop a mechanical model without inflammatory sequelae and how to induce OA without significant experimental trauma and so enable the detection of changes indicative of early-stage OA in the absence of such sequelae. We propose that the most popular post-traumatic OA biomechanical models are not representative of all types of mechanical overloading OA and, in particular, identify a deficiency of current rodent models to represent the chronic overloading OA phenotype without requiring intraarticular surgery. We therefore pinpoint well standardized and reproducible chronic overloading models that are being developed to enable the study of early OA changes in non-trauma related, slowly-progressive OA. In particular, non-invasive models (repetitive small compression loading model and exercise model) and an extra-articular surgical model (osteotomy) are attractive ways to present the chronic natural course of primary OA. Use of these models and quantitative mechanical behaviour tools such as gait analysis and non-invasive imaging techniques show great promise in understanding the mechanical aspects of the onset and progression of OA in the context of chronic knee joint overloading. Further development of these models and the advanced characterisation tools will enable better replication of the human chronic overloading OA phenotype and thus facilitate mechanically-driven clinical questions to be answered.
骨关节炎（OA）是一种常见的慢性疾病，很大程度上由机械因素驱动，在全球范围内造成了重大的健康和经济负担。早期检测具有挑战性，这使得动物模型成为研究其发病机制和与机械相关的发病机理的关键工具。本综述评估了临床前模型和渐进测量技术在分析临床OA表型特定背景下生物力学因素的当前应用。它将临床前模型分为自然发生型、基因改造型、化学诱导型、手术诱导型和非侵入型，并将每种类型与慢性疼痛、炎症和机械过载等临床表型联系起来。具体而言，我们区分了机械因素和生物因素，对机械过载OA表型给出了新的解释，并提出应将其进一步细分为两种亚型，即创伤后和慢性过载性OA。本综述随后总结了OA生物力学研究中的代表性模型和工具。我们强调并确定了如何开发无炎症后遗症的机械模型，以及如何在无明显实验创伤的情况下诱导OA，从而能够在没有此类后遗症的情况下检测出表明早期OA的变化。我们提出，最常用的创伤后OA生物力学模型并不代表所有类型的机械过载性OA，特别是指出当前啮齿动物模型在不进行关节内手术的情况下无法代表慢性过载性OA表型的缺陷。因此，我们确定了正在开发的标准化和可重复的慢性过载模型，以研究非创伤相关、缓慢进展性OA中的早期OA变化。特别是，非侵入性模型（重复小压缩负荷模型和运动模型）和关节外手术模型（截骨术）是呈现原发性OA慢性自然病程的有吸引力的方法。使用这些模型和定量力学行为工具，如步态分析和非侵入性成像技术，在理解慢性膝关节过载情况下OA发病和进展的力学方面显示出巨大的前景。这些模型和先进表征工具的进一步发展将能够更好地复制人类慢性过载性OA表型，从而有助于回答机械驱动的临床问题。
