Christiansen B A, Guilak F, Lockwood K A, Olson S A, Pitsillides A A, Sandell L J, Silva M J, van der Meulen M C H, Haudenschild D R
Department of Orthopaedic Surgery, University of California-Davis Medical Center, USA.
Department of Orthopaedic Surgery, Duke University Medical Center, USA.
Osteoarthritis Cartilage. 2015 Oct;23(10):1627-38. doi: 10.1016/j.joca.2015.05.009. Epub 2015 May 21.
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 (ACL) 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.
骨关节炎(OA)动物模型是在比人类OA更快的时间轴上研究该疾病发展的重要工具。由于有大量基因改造或近交系小鼠品系可供使用,小鼠尤为有用。大多数现有的OA小鼠模型使用关节损伤或其他急性损伤来引发关节退变,代表创伤后骨关节炎(PTOA)。然而,对于哪种损伤方法最能转化为人类OA,目前尚无共识。目前,手术损伤方法最常用于小鼠OA研究;然而,这些方法可能由于手术/侵入性损伤过程本身而产生混杂效应,而非目标关节损伤。非侵入性损伤方法通过外部机械诱导关节损伤来避免这种并发症,无需划破皮肤或破坏关节。在这方面,非侵入性损伤模型对于研究损伤时启动的早期适应性过程可能至关重要,并且可能更能代表机械诱导损伤的人类OA。在过去几年中,已经描述了少数PTOA的非侵入性小鼠模型,包括胫骨软骨下骨关节内骨折、关节软骨的周期性胫骨压缩负荷以及通过胫骨压缩过载导致的前交叉韧带(ACL)断裂。本综述描述了在每种这些非侵入性模型中用于诱导关节损伤的方法,并展示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。