The Pathobiology of the Meniscus: A Comparison Between the Human and Dog

Abstract

Serious knee pain and related disability have an annual prevalence of approximately 25% on those over the age of 55 years. As curative treatments for the common knee problems are not available to date, knee pathologies typically progress and often lead to osteoarthritis (OA). While the roles that the meniscus plays in knee biomechanics are well characterized, biological mechanisms underlying meniscus pathophysiology and roles in knee pain and OA progression are not fully clear. Experimental treatments for knee disorders that are successful in animal models often produce unsatisfactory results in humans due to species differences or the inability to fully replicate disease progression in experimental animals. The use of animals with spontaneous knee pathologies, such as dogs, can significantly help addressing this issue. As microscopic and macroscopic anatomy of the canine and human menisci are similar, spontaneous meniscal pathologies in canine patients are thought to be highly relevant for translational medicine. However, it is not clear whether the biomolecular mechanisms of pain, degradation of extracellular matrix, and inflammatory responses are species dependent. The aims of this review are (1) to provide an overview of the anatomy, physiology, and pathology of the human and canine meniscus, (2) to compare the known signaling pathways involved in spontaneous meniscus pathology between both species, and (3) to assess the relevance of dogs with spontaneous meniscal pathology as a translational model. Understanding these mechanisms in human and canine meniscus can help to advance diagnostic and therapeutic strategies for painful knee disorders and improve clinical decision making.

Meniscus Matrix Remodeling in Response to Compressive Forces in Dogs

“…Taken together, the results of the biomechanical and biochemical analyses suggest that even if the over-compressed meniscus shows a precocious maturation of the resident cells (fibro-chondrocytic-like appearance) and consequently of the matrix (i.e., collagen type II expression, higher GAGs quantity), the lack of a well-organized collagen network leads to the development of an incompetent tissue. The importance of the collagen network in response to the application of tensile forces through the generation of the so-called hoop stress has been previously described [29] as well as the deep association of collagen type II fibers and GAGs [49]; however, to our knowledge, this is the first study that demonstrated the role of the collagen/GAGs relationship in the achievement of the typical anisotropic and elastic behavior of meniscal tissue in response to a compressive stimulus. Moreover, this investigation shows how native meniscal tissue varies under different biomechanical stimuli, producing useful background information for further tissue engineering applications.…”

“…This condition was considered as a vital bioreactor that applies a dynamic compressive force (the alternation of load-and no-load-bearing) in association with a static compression (due to the continuous growth of the bone segments [39], that compressed the meniscus between the femur condyles and the tibial plateau), thus, menisci in this study were always subjected to a kind of compressive force, with no effective relax periods. Mechanical stresses are fundamental for the health and function of the meniscus [29] in both humans and animal models [40] and biomechanical stimuli are essential factors in the maturation of meniscal cells phenotype and in ECM meniscal remodeling, as demonstrated in pigs and sheep [28,41]. Lack of movement leads to disuse atrophy and loss of proteoglycan in mature menisci as reviewed by [42], and to the degeneration and the disappearing of the menisci during embryologic development, as observed in chickens [43].…”

“…Postnatal weight-bearing and joint motion are the principal factors that determine the phenotypical and architectural changes occurring during the maturation process of the meniscus and are implied in determining the orientation of the collagen fibers in humans [1] and the production of GAGs in pigs [11]. Meniscal tears are reported as spontaneous or, more frequently, secondary to anterior cruciate ligament (ACL) deficiency in both human and canine species [29]. The dog is one of the most utilized animal models in meniscal pathology and repair due to the similarity in pathogenesis and anatomy between these two species [29,30].…”

“…Meniscal tears are reported as spontaneous or, more frequently, secondary to anterior cruciate ligament (ACL) deficiency in both human and canine species [29]. The dog is one of the most utilized animal models in meniscal pathology and repair due to the similarity in pathogenesis and anatomy between these two species [29,30]. Nowadays, different techniques are available to achieve meniscus repair (through sutures or implants) or the complete or partial replacement (with allograft or with scaffolds, either synthetic or biological) [31].…”

Large Animal Models in Regenerative Medicine and Tissue Engineering: To Do or Not to Do

“…Dogs also suffer from naturally occurring meniscal pathologies and hence lend themselves as potential translational models to study mechanisms of degeneration or for testing new treatment strategies (Krupkova et al, 2018). The canine meniscus has comparable anatomic features (vascularization, cellularity, collagen structure) and similar permeability to the human (Sweigart et al, 2004;Deponti et al, 2015).…”