A Review of Translational Animal Models for Knee Osteoarthritis

Abstract

Knee osteoarthritis remains a tremendous public health concern, both in terms of health-related quality of life and financial burden of disease. Translational research is a critical step towards understanding and mitigating the long-term effects of this disease process. Animal models provide practical and clinically relevant ways to study both the natural history and response to treatment of knee osteoarthritis. Many factors including size, cost, and method of inducing osteoarthritis are important considerations for choosing an appropriate animal model. Smaller animals are useful because of their ease of use and cost, while larger animals are advantageous because of their anatomical similarity to humans. This evidence-based review will compare and contrast several different animal models for knee osteoarthritis. Our goal is to inform the clinician about current research models, in order to facilitate the transfer of knowledge from the “bench” to the “bedside.”

A rabbit model demonstrates the influence of cartilage thickness on intra‐articular drug delivery and retention within cartilage

“…2,3,8 While rodent models are powerful tools for investigating biological disease mechanisms and initial screening of therapeutics, data from larger animal models are clinically more relevant and generally preferred by the FDA. 2,3 Here, we focus on additional engineering criteria associated with the importance of larger animal models for delivery and retention of drugs within cartilage relevant to OA/PTOA. Simple intra-articular (i.a.)…”

Analysis and selection of experimental models of osteoarthritis

“…For this purpose, different types of animals are used: mouse, rat, dog, horse, sheep, goat, guinea pig, etc. It is important to remember that translation of knowledge from animal models to humans should be done with caution (Gregory et al, 2012).…”

“…So, small animal models are most advantageous for investigation of specifi c disease mechanisms, preclinical initial screening of therapeutics. They, especially mouse models, are useful in elucidating the genetic (for example, Kniest and Sickler syndrome) and molecular pathogenesis of OA (Gregory et al, 2012). In the case of morphological examination of joint, in general, these models are also favorable, because of the size of the joint.…”

Animal Models of Osteoarthritis

“…Rabbits have been popular for chemically and surgically induced models of OA for decades (see early studies 15,38 ) despite the marked differences in joint biomechanics and gait when compared to humans. 31,54 Rabbit stifles have a significantly higher flexion angle than that of humans 127 and, unlike other species (including humans), naturally load the lateral compartment of the femorotibial joint rather than the medial. 75,136 As a result, although surgical interventions in the medial compartment do result in medial lesions, more severe lesions are seen if the intervention is on the lateral side.…”

“…27,54,75 Rabbit cartilage has been reported to exhibit spontaneous healing, particularly in young animals (up to 20 weeks of age). 2,31,54 This may be one reason why induced OA lesions are more severe and develop more rapidly in older rabbits. 117 The issue of spontaneous repair is of particular concern when using rabbits to evaluate methods of cartilage repair.…”