What constitutes an “animal model of osteoarthritis” – the need for consensus?

Abstract

The available data indicates that the molecular mechanisms of both joint structural damage and pain may be distinct in animal models of OA induced or initiated by different means. This suggests the need to continue using multiple OA animal models but that the subsequent interpretation of the data and its extrapolation to the human condition must be more precise.

Animal Models of Osteoarthritis: Challenges of Model Selection and Analysis

“…Interestingly, their review points out that injection OA models are much more frequently used in the study of interventions to reduce OA pain than surgical instability models. Of the 112 studies targeting OA pain included in this review, 67% used injection methods or other methods that induced joint damage that "would not be widely accepted as typical of OA," while only 25% used surgically induced instability (39). This dichotomy, between commonly published animal models of OA pain and those of OA histology, limits the comparison of results between studies of interventions to target OA symptoms and disease progression.…”

Animal Models of Osteoarthritis

“…75,81,136 Each model relies on a combination of joint instability, altered joint mechanics (ie, changes in load bearing or joint congruence), and inflammation to induce OA lesions. 75,136 It is of note that the majority of these procedures are performed in the stiflethe equivalent of the human knee-with the exception of osteochondral chip models in the horse, which are performed in either the carpus (see review 96 ) or the metacarpophalangeal joint.…”

“…122,136 This is largely due to the widespread cell death and rapid joint destruction that occur, particularly secondary to MIA injection, which would not be considered typical for either spontaneous or posttraumatic OA. 81 It is interesting to note that very few studies investigating structural changes of disease, even therapeutic interventions for these structural changes, have evaluated pain. Indeed, since pain occurs late in the disease process, it is considered to not be a feature of most of these models; however, given the evidence suggesting that different mechanisms of injury may result in varied molecular mechanisms of pain, this seems to be a potentially serious oversight.…”

“…Two items in the ARRIVE checklist specifically deal with justification of the selected animal model and recognition of its limitations; thus, consultation of these guidelines during the design phase of an experiment is highly recommended. 81 …”

Extending the Paradigm of Osteoarthritis: Comment on the Editorial by McAlindon

“…The heterogeneity of OA is no better demonstrated than in the excellent study by Roemer et al (7), which reveals a great variation in joint features imaged in the knees of 355 patients and a very complex pattern of change over time. Results from experimental animal studies also provide explicit evidence that OAlike pathology can be induced in joints by vastly different causes, including surgical, genetic, and metabolic causes, and is greatly influenced by background genetics (8,9).…”