A review on current animal models of osteoarthritis research; paving the way for the development of novel disease-modifying anti-osteoarthritic agents

Abstract

Purpose: Osteoarthritis (OA) is one of the most prevalent chronic conditions worldwide. Pathogenesis of idiopathic OA has not yet been fully understood. The time course of disease onset is slow and disease progression is extremely variable. Therefore, the development of OA is difficult to study in humans, and animal models seem to be invaluable research tools that enable the researchers not only to further their understanding of disease pathogenesis but also to pave the way for the development of novel therapeutic agents. The present study aims to review available OA animal models and induction mechanisms. Advantages and disadvantages of the species commonly used and OA induction methods will also be discussed in detail. Methods: The researchers reviewed available OA animal models and induction mechanisms including intra-articular injections of enzymes, and chemicals as well as surgical inductions of OA. Literature searches were conducted on electronic databases, and the following MeSH terms were used: Osteoarthritis animal models, Osteoarthritis Induction Mechanisms, Papain, Collagenase, Hyaluronidase, Monosodium Iodoacetate, Anterior Cruciate Ligament Transection (ACLT), and Meniscectomy. Results: Enzymatically/ chemically induced OA models have found to exhibit various effects on joint physiology. Papain and Monosodium Iodoacetate have found to specifically alter chondrocyte metabolism and induce significant chondrocyte apoptosis and joint inflammation; whereas, collagenase-induced models showed histological damages to ligaments and tendons. However, some studies were skeptical regarding the use of Monosodium Iodoacetate induction method for pathophysiological studies of human OA. Cartilage degeneration in collagenase-induced models is thought to be associated with the direct ingestion of collagen in cartilage and the inflammatory reaction in the joint tissue. However, studies suggested that genetic differences in the composition of proteoglycans and arrangement of collagen fibers may influence the sensitivity of the cartilage. Surgically-induced animal models (ACLT, and Meniscectomy) were found to be one of the most widely used OA induction methods. In comparison with other OA induction methods, surgically-induced OA showed a higher disease onset and disease severity. Most studies reported sequential events of cartilage degeneration, subchondral sclerosis, and osteophyte formation in both rat and rabbit ACLT and Meniscectomy models. The underlying initiating mechanism in surgically-induced OA models was found to be the altered mechanical loading which is the same initiating cause in human secondary OA. Conclusions: All animal models and induction mechanisms result in morphological changes that resemble human pathology in some stages of the disease. Differences are particularly in time of onset of the disease and the speed of disease progression. Moreover, molecular mechanisms of joint structural damage are distinct in different animal models and induction mechanisms. Each animal model and induction mechanism used in OA research has its own advantages and disadvantages. Thus, choosing the best model which mimics human etiology and addresses the aim of the study seems to be a crucial step in conducting research in this area. Hopefully, the present study provides a framework for choosing the best animal model and paves the way for the development of novel disease-modifying agents.