Non-invasive mouse models of post-traumatic osteoarthritis

Abstract

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.

Post-Traumatic Osteoarthritis in Mice Following Mechanical Injury to the Synovial Joint

“…increased pathology at early time points for 6N and 9N groups and at late time points in 9N and 12N groups). In contrast to previous studies on loading model781020, which largely focused on ACL and did not report whether the PCL was effected or not, our study provides bona fide information on PCL injury.…”

“…Any injury severe enough to cause anterior cruciate ligament (ACL) tear and/or meniscus destabilization frequently leads to PTOA456. A consensus has been developed that if we wish to replicate an injury setting in rodents similar to humans, we must consider using a non-invasive injury model that avoids surgery in order to more closely mimic typical knee trauma in humans7891011. A non-invasive injury model of tibial compression−such as the one developed by us10 and others in a modified form7 −is attractive for studying PTOA in mice.…”

A Less Invasive Approach of Medial Meniscectomy in Rat: A Model to Target Early or Less Severe Human Osteoarthritis

“…Using a joint injury to initiate joint degeneration represents post-traumatic OA. 'Less invasion' to 'more invasion' to cause post-traumatic OA may have significant effects due to the surgical/invasive injury procedure itself, rather than the targeted joint injury [29]. We took a less invasive approach on MMx surgery in the rat.…”

The role of subchondral bone damage in post‐traumatic osteoarthritis

“…carried out a comprehensive review of various noninvasive mouse models that have recently been developed . The authors contrast these methods and note that each provides an opportunity to study a particular aspect of PTOA . Our laboratory has developed a noninvasive rat model, which provides an opportunity to study subchondral microdamage .…”