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."

Figure 1

Macroscopic observation and histology of the tibial cartilage of a 3-month-old (a, c) and 12-month-old (b, d) Dunkin Hartley guinea pigs. No cartilage degeneration is observable at 3 months. In contrast, at 12 months, the cartilage is degenerated with erosion and fragmentation on the medial side. Reprinted with permission from [25].

Figure 2

Comparative radiographic (a) and gross (b, c) anatomy of the canine stifle (top row) and human knee (bottom row). The radiographic images show osteoarthritic joints while the gross images show normal patellofemoral joints (b) and normal tibial plateaus (c). The canine stifle joint is approximately 3.5–5 cm from medial to lateral edge for medium to large breed dogs (upper left panel a) compared to approximately 7–10 cm for the human knee joint (lower left panel a) reprinted with permission from [75].

Figure 3

(a, b) Initial and 12-week postoperative arthroscopic views of one dog from each surgical induction model. ACL-T, anterior cruciate ligament transection; GR, groove model; MR, meniscal release; SHAM, manipulation without insult reprinted with permission from [46].