ABSTRACT: Cartilage metabolism-both the synthesis and breakdown of cartilage constituents and architecture-is influenced by its mechanical loading. Therefore, physical activity is often recommended to maintain cartilage health and to treat or slow the progression of osteoarthritis, a debilitating joint disease causing cartilage degeneration. However, the appropriate exercise frequency, intensity, and duration cannot be prescribed because direct in vivo evaluation of cartilage following exercise has not yet been performed. To address this gap in knowledge, we developed a cartilage stress test to measure the in vivo strain response of healthy human subjects' tibial cartilage to walking exercise. We varied both walk duration and speed in a dose-dependent manner to quantify how these variables affect cartilage strain. We found a nonlinear relationship between walk duration and in vivo compressive strain, with compressive strain initially increasing with increasing duration, then leveling off with longer durations. This work provides innovative measurements of cartilage creep behavior (which has been well-documented in vitro but not in vivo) during walking. This study showed that compressive strain increased with increasing walking speed for the speeds tested in this study (0.9-2.0 m/s). Furthermore, our data provide novel measurements of the in vivo strain response of tibial cartilage to various doses of walking as a mechanical stimulus, with maximal strains of 5.0% observed after 60 minutes of walking. These data describe physiological benchmarks for healthy articular cartilage behavior during walking and provide a much-needed baseline for studies investigating the effect of exercise on cartilage health.
Project description:We investigated the relationship between the magnitude and duration of chronic compressive load alteration and the development and progression of degenerative changes in the rabbit tibiofemoral joint. Varus loading devices were attached to the hind limb of mature NZW rabbits. Altered compressive loads of 0%, 50%, and 80% body weight (BW) were applied to the tibiofemoral joint for 12 h per day for 12 and 24 weeks (n?=?4 animals/group). Compartment-specific assessment of the tibial plateau included histological assessments (articular cartilage, calcified cartilage, and subchondral bone thicknesses, degeneration score, and articular cartilage cellularity) and biomechanical measures (aggregate modulus, permeability, Poisson's ratio). Analyses of variance techniques were used to examine the relationship between each outcome measure with load magnitude and duration as independent variables in the model. Degenerative changes developed in the medial compartment with increased magnitude of compressive loading and included fibrillation, increased degeneration score, and reduced cellularity of the articular cartilage. Increased calcified cartilage thickness was observed in both the medial and lateral compartments following exposure to altered loading of 80% BW for 24 weeks. This work demonstrates that in vivo chronic compressive load alteration to the tibiofemoral joint can initiate progressive macroscopic and histological-based degenerative changes analogous to the early changes occurring in OA.
Project description:The physis, or growth plate, is a complex disc-shaped cartilage structure that is responsible for longitudinal bone growth. In this study, a multi-scale computational approach was undertaken to better understand how physiological loads are experienced by chondrocytes embedded inside chondrons when subjected to moderate strain under instantaneous compressive loading of the growth plate. Models of representative samples of compressed bone/growth-plate/bone from a 0.67 mm thick 4-month old bovine proximal tibial physis were subjected to a prescribed displacement equal to 20% of the growth plate thickness. At the macroscale level, the applied compressive deformation resulted in an overall compressive strain across the proliferative-hypertrophic zone of 17%. The microscale model predicted that chondrocytes sustained compressive height strains of 12% and 6% in the proliferative and hypertrophic zones, respectively, in the interior regions of the plate. This pattern was reversed within the outer 300 ?m region at the free surface where cells were compressed by 10% in the proliferative and 26% in the hypertrophic zones, in agreement with experimental observations. This work provides a new approach to study growth plate behavior under compression and illustrates the need for combining computational and experimental methods to better understand the chondrocyte mechanics in the growth plate cartilage. While the current model is relevant to fast dynamic events, such as heel strike in walking, we believe this approach provides new insight into the mechanical factors that regulate bone growth at the cell level and provides a basis for developing models to help interpret experimental results at varying time scales.
Project description: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.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.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.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.
Project description:Functional interpretations of limb bone structure frequently assume that diaphyses adjust their shape by adding bone primarily across the plane in which they are habitually loaded in order to minimize loading-induced strains. Here, to test this hypothesis, we characterize the in vivo strain environment of the sheep tibial midshaft during treadmill exercise and examine whether this activity promotes bone formation disproportionately in the direction of loading in diaphyseal regions that experience the highest strains. It is shown that during treadmill exercise, sheep tibiae were bent in an anteroposterior direction, generating maximal tensile and compressive strains on the anterior and posterior shaft surfaces, respectively. Exercise led to significantly increased periosteal bone formation; however, rather than being biased toward areas of maximal strains across the anteroposterior axis, exercise-related osteogenesis occurred primarily around the medial half of the shaft circumference, in both high and low strain regions. Overall, the results of this study demonstrate that loading-induced bone growth is not closely linked to local strain magnitude in every instance. Therefore, caution is necessary when bone shaft shape is used to infer functional loading history in the absence of in vivo data on how bones are loaded and how they actually respond to loading.
Project description:Charcot-Marie-Tooth (CMT) disease is a hereditary neuropathy associated with impaired walking capacity. Some patients are too weak in the lower extremity muscles to walk at gravity with sufficient intensity or duration to gain benefit.The aim was to investigate the effect of aerobic anti-gravity exercise in weak patients with CMT 1A and X.Five adult patients performed moderate-intensity aerobic anti-gravity exercise 3/week for 10 weeks.There was a significant positive difference in Berg balance scale and postural stability test between test occasions, and walking distance in the 6-min walk test trended to increase.The study indicates that the anti-gravity treadmill training of patients with CMT should be pursued in larger CMT cohorts.
Project description:Focal cartilage lesions can proceed to severe osteoarthritis or remain unaltered even for years. A method to identify high risk defects would be of utmost importance to guide clinical decision making and to identify the patients that are at the highest risk for the onset and progression of osteoarthritis. Based on cone beam computed tomography arthrography, we present a novel computational model for evaluating changes in local mechanical responses around cartilage defects. Our model, based on data obtained from a human knee in vivo, demonstrated that the most substantial alterations around the defect, as compared to the intact tissue, were observed in minimum principal (compressive) strains and shear strains. Both strain values experienced up to 3-fold increase, exceeding levels previously associated with chondrocyte apoptosis and failure of collagen crosslinks. Furthermore, defects at the central regions of medial tibial cartilage with direct cartilage-cartilage contact were the most vulnerable to loading. Also locations under the meniscus experienced substantially increased minimum principal strains. We suggest that during knee joint loading particularly minimum principal and shear strains are increased above tissue failure limits around cartilage defects which might lead to osteoarthritis. However, this increase in strains is highly location-specific on the joint surface.
Project description:Osteoarthritis (OA) is associated with increased articular cartilage hydraulic permeability and decreased maintenance of high interstitial fluid load support (IFLS) during articulation, resulting in increased friction on the cartilage solid matrix. This study assesses frictional response following in situ synthesis of an interpenetrating polymer network (IPN) designed to mimic glycosaminoglycans (GAGs) depleted during OA.Cylindrical osteochondral explants containing various interpenetrating polymer concentrations were subjected to a torsional friction test under unconfined creep compression. Time-varying coefficient of friction, compressive engineering strain, and normalized strain values (?/?eq) were calculated and analyzed.The polymer network reduced friction coefficient over the duration of the friction test, with statistically significantly reduced friction coefficients (95% confidence interval 14-34% reduced) at equilibrium compressive strain upon completion of the test (P = 0.015). A positive trend was observed relating polymer network concentration with magnitude of friction reduction compared to non-treated tissue.The cartilage-interpenetrating polymer treatment improves lubrication by augmenting the biphasic tissue's interstitial fluid phase, and additionally improves the friction dissipation of the tissue's solid matrix. This technique demonstrates potential as a therapy to augment tribological function of articular cartilage.
Project description:Alcohol hangover is a potentially debilitating state. Several studies have demonstrated that it does not seem to impair strength or short-term endurance, but its effects on continuous exercise performance/long-term endurance have never been investigated. Therefore, the aim of the current study was to assess hiking performance of participants who walked the 15.8 km Samaria Gorge in Crete, Greece. Participants completed a survey in the morning before walking the Gorge, and in the afternoon after completion of the walk. Demographics, data on previous evening alcohol consumption, sleep, hangover symptoms, and walking performance were assessed. Data from N=299 participants with a mean (SD) age of 38.9 (11.0) years were analyzed. N=223 participants (74.6%) consumed alcohol the evening before walking the Samaria Gorge, and N= 176 (78.9%) of those reported a hangover. They consumed a mean (SD) of 3.0 (1.8) alcoholic drinks (10 g alcohol each) with a corresponding next-morning hangover severity of 4.6 (2.4) on a 0-10 scale. Participants with a hangover reported feeling significantly more exhausted after the walk compared to participants with no hangover. The groups did not significantly differ in duration of the walk, and the number and duration of breaks. Overall hangover severity, assessed either before, during, or after walking the Samaria Gorge was not significantly correlated with any walking outcome. In conclusion, hungover participants experienced significantly more exhaustion when performing physical activity at the same level as non-hungover participants.
Project description:The aim of this study was to evaluate the safety, feasibility and preliminary effects of a high-intensity rehabilitative task-oriented circuit training (TOCT) in a sample of multiple sclerosis (MS) subjects on walking competency, mobility, fatigue and health-related quality of life (HRQoL).24 MS subjects (EDSS 4.89?±?0.54, 17 female and 7 male, 52.58?±?11.21 years, MS duration 15.21?±?8.68 years) have been enrolled and randomly assigned to 2 treatment groups: (i) experimental group received 10 TOCT sessions over 2 weeks (2 hours/each session) followed by a 3 months home exercise program, whereas control group did not receive any specific rehabilitation intervention. A feasibility patient-reported questionnaire was administered after TOCT. Functional outcome measures were: walking endurance (Six Minute Walk Test), gait speed (10 Meter Walk Test), mobility (Timed Up and Go test) and balance (Dynamic Gait Index). Furthermore, self-reported questionnaire of motor fatigue (Fatigue Severity Scale), walking ability (Multiple Sclerosis Walking Scale - 12) and health-related quality of life (Multiple Sclerosis Impact Scale - 29) were included. Subjects' assessments were delivered at baseline (T0), after TOCT (T1) and 3 months of home-based exercise program (T2).After TOCT subjects reported a positive global rating on the received treatment. At 3 months, we found a 58.33% of adherence to the home-exercise program. After TOCT, walking ability and health-related quality of life were improved (p?<?0.05) with minor retention after 3 months. The control group showed no significant changes in any variables.This two weeks high-intensity task-oriented circuit class training followed by a three months home-based exercise program seems feasible and safe in MS people with moderate mobility impairments; moreover it might improve walking abilities.NCT01464749.
Project description:This study has presented the first purely biomechanical surgical model of osteoarthritis (OA) in rats, which could be more representative of the human primary disease than intra-articular techniques published previously. A surgical tibial osteotomy (TO) was used to induce degenerative cartilage changes in the medial knee of Sprague-Dawley rats. The presence of osteoarthritic changes in the medial knee compartment of the operated animals was evaluated histologically and through analysis of serum carboxy-terminal telepeptides of type II collagen (CTX-II). In-vivo biomechanical analyses were carried out using a musculoskeletal model of the rat hindlimb to evaluate the loading conditions in the knee pre and post-surgically. Qualitative and quantitative medial cartilage degeneration consistent with OA was found in the knees of the operated animals alongside elevated CTX-II levels and increased tibial compressive loading. The potential avoidance of joint inflammation post-surgically, the maintenance of internal joint biomechanics and the ability to quantify the alterations in joint loading should make this model of OA a better candidate for modeling primary forms of the disease in humans.