Non-invasive mouse models of post-traumatic osteoarthritis.

Non-invasive mouse models of post-traumatic osteoarthritis.
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DOI:
10.1016/j.joca.2015.05.009
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发表时间:
2015-10
影响因子:
7
通讯作者:
Haudenschild DR
Haudenschild DR
中科院分区:
医学2区
文献类型:
--
作者:
Christiansen BA;Guilak F;Lockwood KA;Olson SA;Pitsillides AA;Sandell LJ;Silva MJ;van der Meulen MC;Haudenschild DR

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骨关节炎(OA)的动物模型是在比人类OA更快的时间轴上研究疾病发展的重要工具。小鼠是特别有用的,这是由于可用的遗传修饰或近交系小鼠品系过多。大多数可用的OA小鼠模型使用关节损伤或其他急性损伤来引发关节变性,代表创伤后骨关节炎(PTOA)。然而,对于哪种损伤方法最适用于人类OA,还没有达成共识。目前,手术损伤方法最常用于小鼠OA研究;然而,由于手术/侵入性损伤程序本身而不是靶向关节损伤,这些方法可能具有混淆效应。非侵入性损伤方法通过在外部机械诱导关节损伤来避免这种并发症,而不会破坏皮肤或破坏关节。在这方面,非侵入性损伤模型可能是至关重要的研究在受伤时开始的早期适应过程,并可能更代表人类OA的损伤是机械诱导的。在过去的几年中,已经描述了少量的PTOA的非侵入性小鼠模型,包括胫骨软骨下骨的关节内骨折、关节软骨的周期性胫骨压缩负荷和通过胫骨压缩过载导致的前交叉韧带断裂。本文综述了这些非侵入性模型中用于诱导关节损伤的方法,并介绍了利用这些模型的研究结果。总之,这些非侵入性小鼠模型代表了用于研究PTOA不同方面的独特且重要的动物模型谱。
Animal models of osteoarthritis (OA) are essential tools for investigating the development of the disease on a more rapid timeline than human OA. Mice are particularly useful due to the plethora of genetically modified or inbred mouse strains available. The majority of available mouse models of OA use a joint injury or other acute insult to initiate joint degeneration, representing post-traumatic osteoarthritis (PTOA). However, no consensus exists on which injury methods are most translatable to human OA. Currently, surgical injury methods are most commonly used for studies of OA in mice; however, these methods may have confounding effects due to the surgical/invasive injury procedure itself, rather than the targeted joint injury. Non-invasive injury methods avoid this complication by mechanically inducing a joint injury externally, without breaking the skin or disrupting the joint. In this regard, non-invasive injury models may be crucial for investigating early adaptive processes initiated at the time of injury, and may be more representative of human OA in which injury is induced mechanically. A small number of non-invasive mouse models of PTOA have been described within the last few years, including intra-articular fracture of tibial subchondral bone, cyclic tibial compression loading of articular cartilage, and anterior cruciate ligament rupture via tibial compression overload. This review describes the methods used to induce joint injury in each of these non-invasive models, and presents the findings of studies utilizing these models. Altogether, these non-invasive mouse models represent a unique and important spectrum of animal models for studying different aspects of PTOA.