OA foundations - experimental models of osteoarthritis

Abstract

Osteoarthritis (OA) is increasingly recognised as a disease of diverse phenotypes with variable clinical presentation, progression, and response to therapeutic intervention. This same diversity is readily apparent in the many animal models of OA. However, model selection, study design, and interpretation of resultant findings, are not routinely done in the context of the target human (or veterinary) patient OA sub-population or phenotype. This review discusses the selection and use of animal models of OA in discovery and therapeutic-development research. Beyond evaluation of the different animal models on offer, this review suggests focussing the approach to OA-animal model selection on study objective(s), alignment of available models with OA-patient sub-types, and the resources available to achieve valid and translatable results. How this approach impacts model selection is discussed and an experimental design checklist for selecting the optimal model(s) is proposed. This approach should act as a guide to new researchers and a reminder to those already in the field, as to issues that need to be considered before embarking on in vivo pre-clinical research. The ultimate purpose of using an OA animal model is to provide the best possible evidence if, how, when and where a molecule, pathway, cell or process is important in clinical disease. By definition this requires both model and study outcomes to align with and be predictive of outcomes in patients. Keeping this at the forefront of research using pre-clinical OA models, will go a long way to improving the quality of evidence and its translational value.

Keywords: Animal models; Endotype; Experimental design; Osteoarthritis; Phenotype; Pre-clinical; Predictive utility.