The structural organization of a knee, the most complex joint of the human body, dictates its function. The osteochondral unit, a composite of the subchondral bone and the articular cartilage, guarantees its complex biomechanical movements based on an intricate morphology. The subchondral bone is composed of the subchondral bone plate, corresponding to the cortical bone of other skeletal sites, and the trabecular network of the subarticular spongiosa1. It is in the focus of many orthopedic and systemic conditions, including osteoarthritis (OA), osteoporosis, osteopenia, osteonecrosis, osteochondritis dissecans, and fractures2. In the knee, its local interaction is further influenced by the presence (or absence) of the fibrocartilaginous menisci, reflected in bone mineral density8 and microarchitectural differences among which trabecular number and thickness, anisotropy and bone sclerosis. Large and small animal models are critical to model the complex disease mechanisms affecting a functional joint.
Implantation of chondrogenic cells without or with additional biomaterial scaffolds in ectopic locations in vivo generates substitutes of cartilage with structural and functional characteristics that are used in fundamental investigations while also serving as a basis for translational studies. The most relevant ectopic models include subcutaneous, intramuscular, and kidney capsule transplantation. Although the absence of a physiological joint environment and biomechanical stimuli is the major limiting factor, ectopic models are an established component for articular cartilage research aiming to generate a bridge between in vitro data and the clinically more relevant translational orthotopic in vivo models when their limitations are considered. Small animal models are critical to model the complex disease mechanisms affecting a functional joint leading to articular cartilage disorders. They are advantageous for several reasons and significantly contributed to the understanding of the mechanisms of cartilage diseases among which osteoarthritis. This talk summarizes the most relevant anatomical structural and functional characteristics of the knee (stifle) joints of the major small and large animal species, including mice, rats, guinea pigs, rabbits (mini)pigs, sheep, and horses in comparison with humans. Specific characteristics of each species, including kinematical gait parameters are provided and compared with the human situation. Species-dependent differences highly affect the results of a pre-clinical study and need to be considered, necessitating specific knowledge not only of macroscopic and microscopic anatomical and pathological aspects, but also characteristics of their individual gait and joint movements. Considering these multifactorial dimensions will allow to select the appropriate model for answering the research questions in a clinically relevant fashion.
Ann Anat. 2021 Sep;237:151721. doi: 10.1016/j.aanat.2021.151721. Ectopic models recapitulating morphological and functional features of articular cartilage. Xiaoyu Cai, Oliver Daniels, Magali Cucchiarini, Henning Madry. DOI: 10.1016/j.aanat.2021.151721
Comparative anatomy and morphology of the knee in translational models for articular cartilage disorders. Part I: Large animals. Oláh T, Cai X, Michaelis JC, Madry H. Ann Anat. 2021 May;235:151680. doi: 10.1016/j.aanat.2021.151680. Epub 2021 Feb 3. PMID: 33548412
Comparative anatomy and morphology of the knee in translational models for articular cartilage disorders. Part II: Small animals. Oláh T, Michaelis JC, Cai X, Cucchiarini M, Madry H. Ann Anat. 2021 Mar;234:151630. doi: 10.1016/j.aanat.2020.151630. Epub 2020 Oct 29. PMID: 33129976
A comparative study of articular cartilage thickness in the stifle of animal species used in human pre-clinical studies compared to articular cartilage thickness in the human knee. Frisbie DD, Cross MW, McIlwraith CW. Vet Comp Orthop Traumatol. 2006;19(3):142-6. PMID: 16971996
Of mice, men and elephants: the relation between articular cartilage thickness and body mass. Malda J, de Grauw JC, Benders KE, Kik MJ, van de Lest CH, Creemers LB, Dhert WJ, van Weeren PR. PLoS One. 2013;8(2):e57683. doi: 10.1371/journal.pone.0057683. Epub 2013 Feb 21. PMID: 23437402