Aerobic and Resistance Training Attenuate Differently Knee Joint Damage Caused by a High-Fat-High-Sucrose Diet in a Rat Model.

OBJECTIVE: Obesity and associated low-level local systemic inflammation have been linked to an increased rate of developing knee osteoarthritis (OA). Aerobic exercise has been shown to protect the knee from obesity-induced joint damage. The aims of this study were to determine (1) if resistance training provides beneficial metabolic effects similar to those previously observed with aerobic training in rats consuming a high-fat/high-sucrose (HFS) diet and (2) if these metabolic effects mitigate knee OA in a diet-induced obesity model in rats. DESIGN: Twelve-week-old Sprague-Dawley rats were randomized into 4 groups: (1) a group fed an HFS diet subjected to aerobic exercise (HFS+Aer), (2) a group fed an HFS diet subjected to resistance exercise (HFS+Res), (3) a group fed an HFS diet with no exercise (HFS+Sed), and (4) a chow-fed sedentary control group (Chow+Sed). HFS+Sed animals were heavier and had greater body fat, higher levels of triglycerides and total cholesterol, and more joint damage than Chow+Sed animals. RESULTS: The HFS+Res group had higher body mass and body fat than Chow+Sed animals and higher OA scores than animals from the HFS+Aer group. Severe bone lesions were observed in the HFS+Sed and Chow+Sed animals at age 24 weeks, but not in the HFS+Res and HFS+Aer group animals. CONCLOSION: In summary, aerobic training provided better protection against knee joint OA than resistance training in this rat model of HFS-diet-induced obesity. Exposing rats to exercise, either aerobic or resistance training, had a protective effect against the severe bone lesions observed in the nonexercised rats.

Correction: A musculoskeletal finite element model of rat knee joint for evaluating cartilage biomechanics during gait.

[This corrects the article DOI: 10.1371/journal.pcbi.1009398.].

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

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.

A musculoskeletal finite element model of rat knee joint for evaluating cartilage biomechanics during gait.

Abnormal loading of the knee due to injuries or obesity is thought to contribute to the development of osteoarthritis (OA). Small animal models have been used for studying OA progression mechanisms. However, numerical models to study cartilage responses under dynamic loading in preclinical animal models have not been developed. Here we present a musculoskeletal finite element model of a rat knee joint to evaluate cartilage biomechanical responses during a gait cycle. The rat knee joint geometries were obtained from a 3-D MRI dataset and the boundary conditions regarding loading in the joint were extracted from a musculoskeletal model of the rat hindlimb. The fibril-reinforced poroelastic (FRPE) properties of the rat cartilage were derived from data of mechanical indentation tests. Our numerical results showed the relevance of simulating anatomical and locomotion characteristics in the rat knee joint for estimating tissue responses such as contact pressures, stresses, strains, and fluid pressures. We found that the contact pressure and maximum principal strain were virtually constant in the medial compartment whereas they showed the highest values at the beginning of the gait cycle in the lateral compartment. Furthermore, we found that the maximum principal stress increased during the stance phase of gait, with the greatest values at midstance. We anticipate that our approach serves as a first step towards investigating the effects of gait abnormalities on the adaptation and degeneration of rat knee joint tissues and could be used to evaluate biomechanically-driven mechanisms of the progression of OA as a consequence of joint injury or obesity.

Prebiotic and Exercise Do Not Alter Knee Osteoarthritis in a Rat Model of Established Obesity.

OBJECTIVE: Metabolic disturbance is a known risk factor for cardiovascular disease and has been identified as a risk factor for the development of knee osteoarthritis. In this study, we sought to determine the effects of prebiotic fiber supplementation, aerobic exercise, and the combination of the 2 interventions, on the progression of knee osteoarthritis in a high-fat/high-sucrose diet-induced rat model of metabolic disturbance. DESIGN: Twelve-week-old male CD-Sprague-Dawley rats were either fed a standard chow diet, or a high-fat/high-sucrose diet. After 12 weeks on diets, rats consuming the high-fat/high-sucrose diet were randomized into 4 subgroups: a sedentary, an aerobic exercise, a prebiotic fiber supplementation, and an aerobic exercise combined with prebiotic fiber supplementation group. The aerobic exercise intervention consisted of a progressive treadmill training program for 12 weeks, while the prebiotic fiber was added to the high-fat/high-sucrose diet at a dose of 10% by weight for 12 weeks. Outcome measures included knee joint damage, body mass, percent body fat, bone mineral density, insulin sensitivity, and serum lipid profile. RESULTS: Aerobic exercise, or the combination of prebiotic fiber and aerobic exercise, improved select markers of metabolic disturbance, but not knee joint damage. However, these results need to be considered in view of the fact that the chow-fed rats had similar knee OA-like damage as the high-fat/high-sucrose-fed rats. CONCLUSION: Exercise or prebiotics did not increase joint damage and might be good strategies for populations with metabolic knee osteoarthritis to alleviate other health-related problems, such as diabetes or cardiovascular disorders.

Mechanical function of cardiac fibre bundles is partly protected by exercise in response to diet-induced obesity in rats.

Decrements in contractile function resulting from obesity are thought to be major reasons for the link between obesity and cardiovascular disease, while exercise has been shown to improve cardiac muscle contractile function. The purpose of this study was to evaluate cardiac contractile properties following obesity induction and the potential protective effect of exercise. Twelve-week-old rats (n = 30) were organized into either a chow diet or a high-fat, high-sucrose (HFHS) diet group. Following 12 weeks of obesity induction the HFHS group animals were stratified and grouped into sedentary (HFHS+Sed) and exercise (HFHS+Ex) groups for an additional 12 weeks. Following 24 weeks of diet intervention, with 12 weeks of aerobic exercise (25 m/min, 30 min/day, 5 days/week) for the HFHS+Ex group, skinned cardiac fibre bundle testing was used to evaluate cardiac contractile properties. Body fat and mass were significantly greater in the HFHS-fed animals compared with the chow controls (p < 0.043). Hearts from rats in the HFHS+Sed group had significantly greater mass (p < 0.03), significantly slower maximum shortening velocity (p = 0.001), and tended to have lower calcium sensitivity (p = 0.077) and a lower proportion of α-myosin heavy chain composition (p = 0.074) than the sedentary chow animals. However, 12 weeks of moderate aerobic exercise partially prevented these decrements in contractile properties. Novelty Cardiac muscle from animals exposed to an obesogenic diet for 24 weeks had impaired contractile properties compared with controls. Obesity-induced impairment of contractile properties of the heart were partially prevented by a 12-week aerobic exercise regime.

Cardiac ventricular muscle mechanical properties through the first year of life in Sprague-Dawley rats.

Advanced age has been shown to result in decreased compliance, shortening velocity, and calcium sensitivity of the heart muscle. Even though cardiac health has been studied extensively in elderly populations, relatively little is known about cardiac health and age for the first part of adulthood. The purpose of this study was to compare cardiac contractile properties across the first year of life in rats (between 17-53 weeks), corresponding to early to mid-adulthood. Hearts were harvested from rats aged 17-, 24-, 36-, and 53-weeks. Skinned cardiac trabecular fibre bundle testing was used to evaluate active and passive force properties, maximum shortening velocity, calcium sensitivity, and myosin heavy chain isoforms. Maximum active stress production was not different between age groups. Calcium sensitivity increased progressively, while shortening velocity remained unchanged after an increase from 17-and 24-weeks. Passive stiffness decreased between 17- and 24-weeks, but then increased progressively through to 53-weeks. Thus, many of the observed detrimental changes in systolic function (reduced shortening velocity and calcium sensitivity) associated with aging, do not seem to occur in early to mid-adulthood, while early signs of increased diastolic stiffness manifest within 53 weeks of age and may represent a first sign of decreasing heart function and health.

Protective effect of prebiotic and exercise intervention on knee health in a rat model of diet-induced obesity.

Obesity, and associated metabolic syndrome, have been identified as primary risk factors for the development of knee osteoarthritis (OA), representing nearly 60% of the OA patient population. In this study, we sought to determine the effects of prebiotic fibre supplementation, aerobic exercise, and the combination of the two interventions, on the development of metabolic knee osteoarthritis in a high-fat/high-sucrose (HFS) diet-induced rat model of obesity. Twelve-week-old male Sprague-Dawley rats were randomized into five groups: a non-exercising control group fed a standard chow diet, a non-exercising group fed a HFS diet, a non-exercising group fed a HFS diet combined with prebiotic fibre supplement, an exercise group fed a HFS diet, and an exercise group fed a HFS diet combined with prebiotic fibre supplement. Outcome measures included knee joint damage, percent body fat, insulin sensitivity, serum lipid profile, serum endotoxin, serum and synovial fluid cytokines and adipokines, and cecal microbiota. Prebiotic fibre supplementation, aerobic exercise, and the combination of the two interventions completely prevented knee joint damage that is otherwise observed in this rat model of obesity. Prevention of knee damage was associated with a normalization of insulin resistance, leptin levels, dyslipidemia, gut microbiota, and endotoxemia in the HFS-fed rats.

Quantifying the Effects of Different Treadmill Training Speeds and Durations on the Health of Rat Knee Joints.

BACKGROUND: Walking and running provide cyclical loading to the knee which is thought essential for joint health within a physiological window. However, exercising outside the physiological window, e.g. excessive cyclical loading, may produce loading conditions that could be detrimental to joint health and lead to injury and, ultimately, osteoarthritis. The purpose of this study was to assess the effects of a stepwise increase in speed and duration of treadmill training on knee joint integrity and to identify the potential threshold for joint damage. METHODS: Twenty-four Sprague-Dawley rats were randomized into four groups: no exercise, moderate duration, high duration, and extra high duration treadmill exercise. The treadmill training consisted of a 12-week progressive program. Following the intervention period, histologic serial sections of the left knee were graded using a modified Mankin Histology Scoring System. Mechanical testing of the tibial plateau cartilage and RT-qPCR analysis of mRNA from the fat pad, patellar tendon, and synovium were performed for the right knee. Kruskal-Wallis testing was used to assess differences between groups for all variables. RESULTS: There were no differences in cartilage integrity or mechanical properties between groups and no differences in mRNA from the fat pad and patellar tendon. However, COX-2 mRNA levels in the synovium were lower for all animals in the exercise intervention groups compared to those in the no exercise group. CONCLUSIONS: Therefore, these exercise protocols did not exceed the joint physiological window and can likely be used safely in aerobic exercise intervention studies without affecting knee joint health.

Individuals with chronic ankle instability compensate for their ankle deficits using proximal musculature to maintain reduced postural sway while kicking a ball.

The aim of this study was to investigate anticipatory (APA), simultaneous (SPA) and compensatory (CPA) postural adjustments in individuals with and without chronic ankle instability (CAI) as they kicked a ball while standing in a single-leg stance on a stable and unstable surface. Electromyographic activity (EMG) of postural muscles and center of pressure (COP) displacements were calculated and their magnitudes analyzed during the postural adjustment intervals. Additionally, the COP area of sway was calculated over the duration of the whole task. The activities of postural muscles were also studied using principal component analysis (PCA) to identify between-group differences in patterns of muscle activation. The individuals with CAI showed reduced magnitude of EMG at the muscles around the ankle while around the hip the activity was increased. These were associated with a reduction in balance sway across the entire task, as compared with the control group. The PCA revealed that CAI participants assemble different sets of muscle activation to compensate for their ankle instability, primarily activating hip/spine muscles. These results set up potential investigations to examine whether balance control interventions enhance these adaptations or revert them to a normal pattern as well as if any of these changes proactively address recurrent ankle sprain conditions.

Individuals with chronic ankle instability exhibit decreased postural sway while kicking in a single-leg stance.

Individuals with chronic ankle instability (CAI) usually experience deficits in balance control, which increase displacement in the body's center of pressure (COP) when they balance on a single leg. Little is known, however, about whether or not these individuals use the strategies of postural adjustment properly, especially during functional tasks that may predispose them to ankle sprain. The aim of this study was to investigate anticipatory (APA) and compensatory (CPA) postural adjustments in individuals with and without CAI as they kick a ball while standing in a single-leg stance with their ankle in neutral and supinated positions. COP displacements were calculated and their magnitudes (range) analyzed during APA and CPA intervals and over the duration of the whole task, represented by the COP area of sway and mean velocity. The CAI group exhibited a significant decrease in CPA and area of sway over the whole task, relative to controls. These results suggest that the decreased balance sway could be caused by the need for further stabilization of the ankle in more unstable postures to prevent recurrent sprain. Our findings could help clinicians to better understand the strategies of postural adjustments in individuals with CAI, and may assist and motivate new investigations into balance control interventions in such individuals, as well as proactively address recurrent ankle sprain conditions.

Ajustes posturais antecipatórios e compensatórios ao pegar uma bola em condição de estabilidade e instabilidade postural / Anticipatory and compensatory postural adjustments during catching a ball in condition of postural instability and stability

Indivíduos jovens pré-selecionam suas estratégias de ajuste postural antes que uma perturbação externa ocorra, com base nas características da tarefa. Entretanto, ainda não é bem conhecido de que maneira o sistema nervoso central lida com os ajustes posturais antecipatórios e compensatórios, mediante alguns treinos de equilíbrio que são comumente usados na prática clínica da Fisioterapia. Treze adultos jovens receberam 20 perturbações posturais externas de pegar uma bola arremessada pelo experimentador sobre condições de estabilidade e instabilidade postural (sobre uma espuma). As atividades eletromiográficas dos músculos tríceps braquial (músculo focal), retoabdominal e paravertebral lombar foram avaliadas nas janelas de tempo típicas dos ajustes posturais antecipatórios e compensatórios, assim como o pico do deslocamento do centro de pressão corporal após a perturbação. A magnitude das integrais da atividade eletromiográfica do músculo tríceps braquial foi significativamente menor em condição de instabilidade postural, não houve diferença estatística entre as condições para as integrais da atividade eletromiográfica dos músculos retoabdominal e paravertebral lombar. O pico do deslocamento anteroposterior do centro de pressão corporal foi similar entre as duas condições. Treino de equilíbrio associado à perturbação externa da postura sobre espuma pode não ser mais eficaz ou eficiente do que sobre uma superfície estável, quando se pretende alterar a atividade dos músculos posturais do tronco. Além disso, este tipo de intervenção pode corroborar para diminuir a ativação antecipatória (ajustes posturais antecipatórios) do músculo focal.

Young individuals preselect their postural adjustment strategies before an external perturbation, based on the characteristics of the task. However, it is not well documented how the central nervous system deals with anticipatory and compensatory postural adjustments during some balance training programs, which are commonly used in Physical Therapy settings. Thirteen young individuals were submitted to 20 external postural perturbations of catching a ball thrown by an experimenter in conditions of postural stability and instability (standing on a foam). The electromyographic activities of triceps brachii (focal muscle), rectus abdominis, and lumbar paraspinal muscles were investigated in the time windows typical for anticipatory and compensatory postural adjustments, as well as the center of body pressure peak displacement after the perturbation. The magnitude of the triceps brachii integral electromyographic activity was significantly smaller in conditions of postural instability, there was no statistical difference between the stable and unstable conditions for the integral electromyographic activity of the rectus abdominis, and lumbar paraspinal muscles. The peak of the center of body pressure anterior posterior displacement was similar between the two conditions. Balance training associated with external perturbation standing on a foam might not be more effective or efficient than when standing on a stable surface, when it seeks to modify the activity of the postural trunk muscles. In addition, this balance training may contribute to decrease the electromyographic activity (anticipatory postural adjustments) of the focal muscle.