Chapter 64Models of Equine Joint Disease Chris E. Kawcak Animals have been used extensively as models of joint disease to study clinical conditions in people. However, veterinary researchers have the luxury of using experimental animals from species that are clinically relevant. Unlike in human research, one has no need to assume similarity in findings between species. Equine models of joint disease have been used for several decades to test the effects of drugs and various treatments on joints and to evaluate the pathogenesis of certain diseases. Joint disease can be assessed in horses with clinical disease; however, large numbers are needed for each treatment group to see significant statistical differences in the face of great variation among individual horses. Owner compliance, differing treatment protocols among clinicians, and variability among horses in response to disease and treatment, as well as conformation, limb use, and size, all contribute to this variation. Furthermore, clinical studies take a long time to perform, and the effects of treatment take a long time to be seen. Consequently, in vitro and in vivo models have been developed to give researchers better-controlled studies that can be done in a relatively short time. The model to be used should be designed to answer a question by using a testable hypothesis. Variability should be reduced as much as possible so that the question can be answered with little outside influence. However, as more and more variables are eliminated, the model becomes less representative of the clinical situation. For instance, the efficacy of oral joint supplements in reducing joint disease cannot rely solely on results from in vitro studies. The drugs must be tested in vivo to determine if and how they work. However, to determine the effects of a drug or chemical on articular cartilage matrix metabolism, a quick, relatively inexpensive in vitro test can be conducted. Therefore the type of model to be used depends on the question to be answered. Two types of models are used to study equine joint disease. In vitro models can be used to study various treatments, using cells, cell lines, or tissues harvested from joints to test usually one specific pathological pathway or treatment scheme. In vivo systems can be used to test drugs and to determine the pathophysiological response to an insult. Unlike in vitro studies, in vivo studies involve the entire joint, allowing researchers to assess the whole organ to determine truly the clinical efficacy of a drug. In this chapter the complexity of joint disease and the use of joint models are discussed. The difficulties in modeling joint disease, the rationale for selecting specific models, specific examples of models used for the study of the joint disease, and the current status and future use of equine models of joint disease are considered. Complexity of Joint Disease The joint can be considered an organ because it is composed of several different types of tissues that biomechanically and biochemically interact with each other. Joint disease can result from several factors. First, the disease has a direct biochemical effect on all tissues. For instance, with synovitis, inflammatory mediators can be released into the joint space and put the articular cartilage into a catabolic state.1-4 Second, the pain produced by joint disease can result in a change in the character of the gait.5,6 Consequently this change in joint loading alters biomechanical inputs on all tissues, resulting in a biochemical change in the response by tissues.7,8 Third, disease of one tissue can result in a change in the mechanical input on another tissue. For instance, articular cartilage degeneration, which can result in increased stress to subchondral bone, can induce a sclerotic response.9 As another example, subchondral bone sclerosis, which commonly occurs in racehorses, can lead to increased stress on overlying articular cartilage.10 Therefore in the live horse all tissues are affected by one another. Because several factors can influence joint disease, researchers have attempted to control these influences in experimental studies. However, not all of the factors can be controlled. For instance, several mechanical factors play a role in joint disease; specifically, mechanical input can vary with horse size, exercise intensity, conformation, neurological control, and lameness. Consequently, differences in the stress to joints can result in changes in biochemical pathways in those tissues. For instance, ponies are one third to one half the size of horses and have little naturally occurring joint disease. Therefore they may not be the best equine models of joint disease for joint healing studies and exercise studies because of lower imposed stresses. However, they are still good models if imposed stresses do not play a role in the specific disease being studied, such as induced synovitis models. Tissue material properties also have an influence on joint disease. For instance, weaker tissues undergo greater biomechanical changes than those that are stronger. Factors that control material properties of tissues include genetics, loading history, and age of the animal. The tissue remodeling status and the ability of horses to remodel articular cartilage, subchondral bone, and soft tissues can also influence joint disease, which is also affected by age, loading history, and genetics. The inflammatory response can also change the joint environment. Specifically, differences in the immune system at the time of disease can greatly influence the inflammatory response to the joint and influence the concentration of cytokines released into the joint. Variables such as age, size, conformation, and neurological status can be controlled in experimental in vivo studies. However, loading history and the presence of subclinical disease are virtually impossible to control. With the advent of more sophisticated imaging equipment, such as computed tomography (CT) and magnetic resonance imaging (MRI), more information on loading history and subclinical disease can be obtained. For instance, subchondral bone density is indicative of loading history.11 Therefore researchers at the Equine Orthopaedic Research Center (EORC) at Colorado State University often perform prestudy CT examinations to determine subchondral bone density as an indicator of loading history. Another benefit of CT and MRI is that some subclinical diseases may be more easily detectable. Researchers at the EORC also initiate a controlled exercise program on a high-speed treadmill before starting the study. The hope is that this can normalize the loading histories of experimental horses. Equally important as loading history and subclinical disease is the biomechanical and biochemical status of the articular cartilage, which at this time is difficult to assess noninvasively at the beginning of a project. With the advent of MRI and pressure probes, articular cartilage and bone matrix structure can be assessed more readily. Types of Models In Vitro Models Only gold members can continue reading. 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Chapter 64Models of Equine Joint Disease Chris E. Kawcak Animals have been used extensively as models of joint disease to study clinical conditions in people. However, veterinary researchers have the luxury of using experimental animals from species that are clinically relevant. Unlike in human research, one has no need to assume similarity in findings between species. Equine models of joint disease have been used for several decades to test the effects of drugs and various treatments on joints and to evaluate the pathogenesis of certain diseases. Joint disease can be assessed in horses with clinical disease; however, large numbers are needed for each treatment group to see significant statistical differences in the face of great variation among individual horses. Owner compliance, differing treatment protocols among clinicians, and variability among horses in response to disease and treatment, as well as conformation, limb use, and size, all contribute to this variation. Furthermore, clinical studies take a long time to perform, and the effects of treatment take a long time to be seen. Consequently, in vitro and in vivo models have been developed to give researchers better-controlled studies that can be done in a relatively short time. The model to be used should be designed to answer a question by using a testable hypothesis. Variability should be reduced as much as possible so that the question can be answered with little outside influence. However, as more and more variables are eliminated, the model becomes less representative of the clinical situation. For instance, the efficacy of oral joint supplements in reducing joint disease cannot rely solely on results from in vitro studies. The drugs must be tested in vivo to determine if and how they work. However, to determine the effects of a drug or chemical on articular cartilage matrix metabolism, a quick, relatively inexpensive in vitro test can be conducted. Therefore the type of model to be used depends on the question to be answered. Two types of models are used to study equine joint disease. In vitro models can be used to study various treatments, using cells, cell lines, or tissues harvested from joints to test usually one specific pathological pathway or treatment scheme. In vivo systems can be used to test drugs and to determine the pathophysiological response to an insult. Unlike in vitro studies, in vivo studies involve the entire joint, allowing researchers to assess the whole organ to determine truly the clinical efficacy of a drug. In this chapter the complexity of joint disease and the use of joint models are discussed. The difficulties in modeling joint disease, the rationale for selecting specific models, specific examples of models used for the study of the joint disease, and the current status and future use of equine models of joint disease are considered. Complexity of Joint Disease The joint can be considered an organ because it is composed of several different types of tissues that biomechanically and biochemically interact with each other. Joint disease can result from several factors. First, the disease has a direct biochemical effect on all tissues. For instance, with synovitis, inflammatory mediators can be released into the joint space and put the articular cartilage into a catabolic state.1-4 Second, the pain produced by joint disease can result in a change in the character of the gait.5,6 Consequently this change in joint loading alters biomechanical inputs on all tissues, resulting in a biochemical change in the response by tissues.7,8 Third, disease of one tissue can result in a change in the mechanical input on another tissue. For instance, articular cartilage degeneration, which can result in increased stress to subchondral bone, can induce a sclerotic response.9 As another example, subchondral bone sclerosis, which commonly occurs in racehorses, can lead to increased stress on overlying articular cartilage.10 Therefore in the live horse all tissues are affected by one another. Because several factors can influence joint disease, researchers have attempted to control these influences in experimental studies. However, not all of the factors can be controlled. For instance, several mechanical factors play a role in joint disease; specifically, mechanical input can vary with horse size, exercise intensity, conformation, neurological control, and lameness. Consequently, differences in the stress to joints can result in changes in biochemical pathways in those tissues. For instance, ponies are one third to one half the size of horses and have little naturally occurring joint disease. Therefore they may not be the best equine models of joint disease for joint healing studies and exercise studies because of lower imposed stresses. However, they are still good models if imposed stresses do not play a role in the specific disease being studied, such as induced synovitis models. Tissue material properties also have an influence on joint disease. For instance, weaker tissues undergo greater biomechanical changes than those that are stronger. Factors that control material properties of tissues include genetics, loading history, and age of the animal. The tissue remodeling status and the ability of horses to remodel articular cartilage, subchondral bone, and soft tissues can also influence joint disease, which is also affected by age, loading history, and genetics. The inflammatory response can also change the joint environment. Specifically, differences in the immune system at the time of disease can greatly influence the inflammatory response to the joint and influence the concentration of cytokines released into the joint. Variables such as age, size, conformation, and neurological status can be controlled in experimental in vivo studies. However, loading history and the presence of subclinical disease are virtually impossible to control. With the advent of more sophisticated imaging equipment, such as computed tomography (CT) and magnetic resonance imaging (MRI), more information on loading history and subclinical disease can be obtained. For instance, subchondral bone density is indicative of loading history.11 Therefore researchers at the Equine Orthopaedic Research Center (EORC) at Colorado State University often perform prestudy CT examinations to determine subchondral bone density as an indicator of loading history. Another benefit of CT and MRI is that some subclinical diseases may be more easily detectable. Researchers at the EORC also initiate a controlled exercise program on a high-speed treadmill before starting the study. The hope is that this can normalize the loading histories of experimental horses. Equally important as loading history and subclinical disease is the biomechanical and biochemical status of the articular cartilage, which at this time is difficult to assess noninvasively at the beginning of a project. With the advent of MRI and pressure probes, articular cartilage and bone matrix structure can be assessed more readily. Types of Models In Vitro Models Only gold members can continue reading. Log In or Register to continue Share this:Click to share on Twitter (Opens in new window)Click to share on Facebook (Opens in new window) Related Related posts: Lameness in Horses: Basic Facts Before Starting Thermography: Use in Equine Lameness Gene Therapy Arthroscopic Examination Stay updated, free articles. Join our Telegram channel Join Tags: Diagnosis and Management of Lameness in the Horse Jun 4, 2016 | Posted by admin in EQUINE MEDICINE | Comments Off on Models of Equine Joint Disease Full access? Get Clinical Tree
