Department of Orthopedics, Anschutz Medical Campus, University of Colorado, Aurora, CO, USA.
Cell Biology, Stems Cells and Development Program, Anschutz Medical Campus, University of Colorado, Aurora, CO, USA.
Methods Mol Biol. 2021;2230:91-103. doi: 10.1007/978-1-0716-1028-2_6.
Given the prevalence and the scope of the personal and societal burden of osteoarthritis (OA), investigators continue to be deeply interested in understanding the pathogenic basis of disease and developing novel disease modifying OA therapies. Because joint trauma/injury is considered a leading predisposing factor in the development of OA, and since posttraumatic OA is one of the most common forms of OA in general, large animal and rodent models of knee injury that accurately recapitulate the OA disease process have become increasingly widespread over the past decade. To enable study in the context of defined genetic backgrounds, investigative teams have developed standardized protocols for injuring the mouse knee that aim to induce a reproducible degenerative process both in terms of severity and temporal pacing of disease progression. The destabilization of the medial meniscus (DMM) is one of the most commonly employed surgical procedure in rodents that reproducibly models posttraumatic OA and allows for the study of disease progression from initiation to end-stage disease. The description provided here sets the stage for both inexperienced and established investigators to employ the DMM procedure, or other similar surgical destabilization methods, to initiate the development of posttraumatic OA in the mouse. Successful application of this method provides a preclinical platform to study the mechanisms driving the pathogenesis of posttraumatic OA and for testing therapeutic strategies to treat it.
鉴于骨关节炎 (OA) 的普遍性和对个人及社会的负担，研究人员仍在深入研究疾病的发病基础，并开发新的治疗 OA 的方法。由于关节创伤/损伤被认为是 OA 发展的主要诱发因素，而创伤后 OA 通常是最常见的 OA 形式之一，因此，过去十年中，能够准确重现 OA 疾病过程的大型动物和啮齿动物膝关节损伤模型已经越来越广泛。为了能够在明确的遗传背景下进行研究，研究小组制定了损伤小鼠膝关节的标准化方案，旨在诱导具有可重复性的退行性过程，无论疾病进展的严重程度还是时间节奏如何。内侧半月板不稳定 (DMM) 是最常用于啮齿动物的手术之一，可重现创伤后 OA，并可研究从发病到终末期疾病的疾病进展。本文的描述为经验丰富和经验不足的研究人员提供了一个框架，以采用 DMM 手术或其他类似的手术不稳定方法，在小鼠中引发创伤后 OA 的发展。成功应用该方法为研究驱动创伤后 OA 发病机制的机制以及测试治疗策略提供了一个临床前平台。
