Animal Models of Osteoarthritis Part 1–Preclinical Small Animal Models: Challenges and Opportunities for Drug Development

Abstract

Osteoarthritis (OA) is the most common form of arthritis and a major source of pain and disability in the adult population. There is a significant unmet medical need for the development of effective pharmacological therapies for the treatment of OA. In addition to spontaneously occurring animal models of OA, many experimental animal models have been developed to provide insights into mechanisms of pathogenesis and progression. Many of these animal models are also being used in the drug development pipeline. Here, we provide an overview of commonly used and emerging preclinical small animal models of OA and highlight the strengths and limitations of small animal models in the context of translational drug development. There is limited information in the published literature regarding the technical reliability of these small animal models and their ability to accurately predict clinical drug development outcomes. The cost and complexity of the available models however is an important consideration for pharmaceutical companies, biotechnology startups, and contract research organizations wishing to incorporate preclinical models in target validation, discovery, and development pipelines. Further considerations relevant to industry include timelines, methods of induction, the key issue of reproducibility, and appropriate outcome measures needed to objectively assess outcomes of experimental therapeutics. Preclinical small animal models are indispensable tools that will shine some light on the pathogenesis of OA and its molecular endotypes in the context of drug development. This paper will focus on small animal models used in preclinical OA research. © 2022 The Authors. Current Protocols published by Wiley Periodicals LLC.

Potentiating TRPA1 by Sea Anemone Peptide Ms 9a-1 Reduces Pain and Inflammation in a Model of Osteoarthritis

“…Osteoarthritis (OA) is the most common form of arthritis and a major source of pain and disability in the adult population [32][33][34]. Inflammation-induced hyperalgesic responses could be reduced by analgesics that decrease nociceptors sensitization and spontaneous activation [35].…”

Mechanical loading and orthobiologic therapies in the treatment of post-traumatic osteoarthritis (PTOA): a comprehensive review

“…It is important to note that while both human and animal research can provide valuable insight into the role of mechanical loading on PTOA development, there are physiological differences in load bearing and anatomy between species, which is a major limitation when using animal models. Certain small animal models have been specifically designed and employed to investigate PTOA ( Little and Hunter, 2013 ; Rios et al, 2022 ; Blaker et al, 2017 ). Small animals are favored due to their simplicity and cost-effectiveness.…”

“…Small animals are favored due to their simplicity and cost-effectiveness. Doubts persist regarding their predictive accuracy, primarily because novel therapeutic effectiveness demonstrated in preclinical studies often fails to translate to human clinical trials ( Rios et al, 2022 ; Malfait and Tortorella, 2019 ). Larger animal models offer advantages due to their anatomical resemblance to humans, thus enhancing their potential for translational research ( Rios et al, 2022 ; Gregory et al, 2012 ).…”

Regenerative Effect of Mesenchymal Stem Cell on Cartilage Damage in a Porcine Model

“…Knee osteoarthritis (OA) is a degenerative joint disease that affects both humans and animals, resulting in significant pain and disability with economic loss [1][2][3]. The progressive degradation of articular cartilage is a significant process for the progression of OA.…”