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Background: As inter-limb asymmetries can be associated with higher injury risk, we aimed to investigate their role in Achilles tendinopathy patients. Methods: In Achilles tendinopathy patients (n = 41), we assessed inter-limb asymmetries of mechanical, material, and morphological musculoskeletal properties and function and how those were affected by 12 weeks of exercise intervention (high-load protocol, n = 13; Alfredson protocol, n = 11). Moreover, we assessed whether asymmetry reductions correlated with improved Patient-Reported Outcomes (VISA-A score). Results: At baseline, tendinopathic tendons demonstrated lower tendon force (p = 0.017), lower tendon stress (p < 0.0001), larger tendon cross-sectional area (CSA) (p < 0.001), and increased intratendinous (p = 0.042) and tendon overall (p = 0.021) vascularization. For the high-load group, PRE-to-POST asymmetry comparisons revealed an asymmetry increase for the counter-movement jump (CMJ) (p = 0.034) and PRE-to-POST VISA-A score improvements correlated with CSA asymmetry reductions (p = 0.024). Within the Alfredson group, PRE-to-POST VISA-A score improvements correlated with CMJ asymmetry reductions (p = 0.044) and tendon stiffness asymmetry increases (p = 0.037). POST-to-POST in-between group comparisons revealed lower asymmetry in the high-load group for tendon elongation (p = 0.021) and tendon strain (p = 0.026). Conclusions: The tendinopathic limb differs from the asymptomatic limb while therapeutic exercise interventions have little effect on asymmetries. Asymmetry reductions are not necessarily associated with tendon health improvements. Federal Institute of Sport Science (BISp) Germany foundation Stiftung Oskar-Helene-Heim, Berlin, Germany

The search strategy of Meta-anaalysis.

Background: Shear Wave Elastography (SWE) is currently used to detect tissue pathologies. For preventive medicine, it may also be applied to uncover structural changes early on before they lead to functional impairment. Hence, it is important to examine the sensitivity of SWE and to investigate how stiffness measures are affected by methodological variables.Objective: To evaluate the acute effects of exercise activity on tendon and muscle stiffness measured by SWE.Methods: Standardized SWE examination of both lower limb tendon and muscles (achilles tendon (AT), Musculus soleus insertion (MS) and Musculus gastrocnemius (MG)) in longitudinal plane were performed in 24 healthy professional female athletes. Measurements were taken before and after a standardized treadmill exercise test. Baseline characteristics and parameters of performance were acquired. Results: In the overall cohort, baseline SWE assessment demonstrated a moderate to strong correlation between pre-exercise and post-exercise stiffness for MS (r=0.613), MG (r=0.609) and AT (r=0.583). In both muscles (Musculus soleus insertion and Musculus gastrocnemius) and achilles tendon, the linear regression shows an increase in stiffness for lower pre-exercise values and decreasing stiffness for higher pre-exercise values. This covariance between pre-exercise values and changes in stiffness is highly significant (pConclusion: SWE measurement revealed that in professional athletes acute exercise induces individually different tissue stiffness changes. Differences and changes of stiffness in professional athletes after acute exercise needed to be considered for diagnosing tendinopathy and injuries. More precise and comparable research protocols in MSK-SWE may be of great benefit for sports medicine but also for rehabilitation and preventive medicine.

Background Assuming that the mechanisms inducing adaptation in healthy tendons yield similar responses in tendinopathic tendons, we hypothesized that a high-loading exercise protocol that increases tendon stiffness and cross-sectional area in male healthy Achilles tendons may also induce comparable beneficial adaptations in male tendinopathic Achilles tendons in addition to improving pain and function. Objectives We investigated the effectiveness of high-loading exercise in Achilles tendinopathy in terms of inducing mechanical (tendon stiffness, maximum strain), material (Young’s modulus), morphological (tendon cross-sectional area (CSA)), maximum voluntary isometric plantar flexor strength (MVC) as well as clinical adaptations (Victorian Institute of Sports Assessment—Achilles (VISA-A) score and pain (numerical rating scale (NRS))) as the primary outcomes. As secondary outcomes, drop (DJ) and counter-movement jump (CMJ) height and intratendinous vascularity were assessed. Methods We conducted a controlled clinical trial with a 3-month intervention phase. Eligibility criteria were assessed by researchers and medical doctors. Inclusion criteria were male sex, aged between 20 and 55 years, chronic Achilles tendinopathy confirmed by a medical doctor via ultrasound-assisted assessment, and a severity level of less than 80 points on the VISA-A score. Thirty-nine patients were assigned by sequential allocation to one of three parallel arms: a high-loading intervention (training at ~ 90% of the MVC) (n = 15), eccentric exercise (according to the Alfredson protocol) as the standard therapy (n = 15) and passive therapy (n = 14). Parameters were assessed pre- and-post-intervention. Data analysis was blinded. Results Primary outcomes: Plantar flexor MVC, tendon stiffness, mean CSA and maximum tendon strain improved only in the high-loading intervention group by 7.2 ± 9.9% (p = 0.045), 20.1 ± 20.5% (p = 0.049), 8.98 ± 5.8% (p p = 0.001), respectively. Stiffness decreased in the passive therapy group (−7.7 ± 21.2%; p = 0.042). There was no change in Young’s modulus in either group (p > 0.05). The VISA-A score increased in all groups on average by 19.8 ± 15.3 points (p p p = 0.005). There was no change in DJ height and vascularity (p > 0.05) in either group. Conclusion Despite an overall clinical improvement, it was exclusively the high-loading intervention that induced significant mechanical and morphological adaptations of the plantar flexor muscle–tendon unit. This might contribute to protecting the tendon from strain-induced injury. Thus, we recommend the high-loading intervention as an effective (alternative) therapeutic protocol in Achilles tendinopathy rehabilitation management in males. Clinical Trials Registration Number: NCT02732782.

Legerlotz, K, Kittelmann, J, Dietzel, M, Wolfarth, B, and Böhlke, N. Ice hockey-specific repeated shuttle sprint test performed on ice should not be replaced by off-ice testing. J Strength Cond Res 36(4): 1071-1076, 2022-Although the importance of sport-specific testing has been stated in various studies, the application of standard tests that are little related to the requirements in competition is still widespread in performance diagnostics. Furthermore, the actual exercise mode in testing often deviates from the exercise mode in competition. The aim of this study was therefore to investigate how the performance in an ice hockey mimicking repeated sprint shuttle test conducted off-ice (RSS) differs from the on-ice performance (RISS). The two performance tests were completed by 21 male junior ice hockey players within one week. Anaerobic fatigue was significantly larger in RISS and did not correlate with RSS, whereas best run, mean run, total run time, turn and fly time, and total times in all three shifts correlated moderately. Although the best and mean run times did not differ, these times were achieved with different strategies depending on the test condition, indicated by significantly different split times. Aerobic fatigue in shift 3 was the only parameter where the off-ice measurement correlated strongly with the on-ice measurement. Our results imply that an off-ice test does not predict on-ice performance with sufficient precision, strongly advocating performance testing in the exercise mode used in competition.

The Kerlan-Jobe Orthopedic Clinic Shoulder and Elbow Score (KJOC) originally developed in English, assesses the functional status of the shoulder and elbow in overhead athletes. To date, no German version of the questionnaire exists.The aim of the study was to translate and to culturally adapt the KJOC into German (KJOC-G) and to test its psychometric properties.The first part of the study consisted of a translation and cross-cultural adaptation process which was performed in six stages according to international recommendations: Initial translations, synthesis, back translations, expert committee review, pretesting of the prefinal version, and final adaptations. Secondly, reliability, validity, and feasibility of the KJOC-G were assessed in German overhead athletes.The translation and adaptation process led to minor alterations due to cultural differences while maintaining the general structure and content of the original score. A total of 152 overhead athletes (age 25.0 ± 6.6 years; 87 men/65 women) were included in the main analyses. The internal consistency (Cronbach's alpha = 0.93) and test-retest reliability (ICCThe KJOC-G score is valid, reliable, and suitable for assessing the functional shoulder and elbow status in German-speaking overhead athletes.

Purpose Physical and hormonal changes during pregnancy are thought to affect balance and injury risk, with increased numbers of falls being reported. A maternity support belt (MSB) has been suggested to stabilize the pelvis and to enhance balance. The purpose of this study was therefore to investigate the effect of an MSB on postural stability in different trimesters of pregnancy. Methods Postural stability was assessed in the first (T1, n = 30), second (T2, n = 30) and third trimester (T3, n = 30) of pregnancy and compared to non-pregnant controls (n = 30), using a portable force plate. Postural sway during quiescent standing with and without applying an MSB was characterized by analyzing path length, velocity, amplitudes and area. Subsequently, anterior and posterior limits of stability (LoS) were determined. Results Postural sway during quiescent standing did not change with pregnancy. However, LoS performance was reduced already in T1, before body mass significantly increased. The MSB led to a small improvement in the LoS while slightly increasing postural sway in anterior-posterior direction and shifting the center of pressure posteriorly during quiescent standing. Conclusion While impairments in balance already occurred early in pregnancy before body mass significantly increased, they were subtle and only measurable in exacerbated conditions. This challenges the assumed necessity of balance enhancing interventions in pregnant women. Although the MSB significantly affected body posture, the magnitude of the LoS improvement using the MSB was very small. Thus, it remains debatable if the MSB is a meaningful tool to increase balance during pregnancy.

The assessment of muscle architecture with B-mode ultrasound is an established method in muscle physiology and mechanics. There are several manual, semi-automated and automated approaches available for muscle architecture analysis from ultrasound images or videos. However, most approaches have limitations such as workload, subjectivity, drift or they are applicable to short muscle fascicles only. Addressing these issues, an algorithm was developed to analyse architectural parameters of the vastus lateralis muscle (VL). In 17 healthy young men and women, ultrasound images were taken five times on two different days during passive knee joint flexion. From the images, fascicle length (FL), pennation angle (PAN) and muscle thickness (MTH) were calculated for both test days using the algorithm. Interday differences were determined using a two-way ANOVA. Interday and intraday reliability were assessed using intraclass correlation coefficients (ICC) and root mean square (RMS) differences. FL, MTH and PAN did not differ between day one and two. The within day ICCs were above 0.94 for all tested parameters. The average interday ICCs were 0.86 for the FL, 0.96 for MTH and 0.60 for PAN. The average RMS differences between both days were 5.0%, 8.5% and 12.0% for MTH, FL and PAN, respectively. The proposed algorithm provides high measurement reliability. However, the interday reliability might be influenced by small differences in probe position between days.

Purpose:To understand the mechanisms for the effects of resistance training on functional parameters, and to assess the injury risk of the involved tissues, it is necessary to examine the underlying morphological and structural changes of the respective tissues.Methods:The presented information on physiological adaptations have been deduced from cross-sectional studies comparing youth athletes with controls and children with adults as well as from longitudinal studies examining the effects of resistance training in untrained children and adolescents and in youth athletes.Results:The evidence indicates, that training induced changes in motor performance rely partly on enhanced neuromuscular control, and partly on morphological adaptation of muscles and tendons, such as changes in muscle, muscle fiber and tendon cross-sectional area, muscle composition, and tendon material properties, with the bone also adapting by increasing bone mineral content and cortical area.Conclusion:Although the training induced adaptations of the investigated tissues follows similar principles in children as in adults, the magnitude of the adaptive response appears to be more subtle. As studies investigating physiological adaptation in youth athletes are sparse, more research in this area is warranted to elucidate the specific physiological stimulus-response relationship necessary for effective training programs and injury prevention.

While the incidence of falls has been described to increase with pregnancy, the mechanism behind this is unclear. Pregnancy associated changes in lower extremity muscle strength could be a possible factor influencing injury risk. Thus, the aim of this longitudinal study was to investigate muscle strength and architectural properties of the lower limbs in different stages of pregnancy and postpartum. In nineteen pregnant women (30 ± 4 years) and fifteen non-pregnant controls (28 ± 4 years) muscle strength and architectural properties of the vastus lateralis muscle were assessed combining dynamometry, ultrasound, kinematic, and electromyographic measurements. Body mass and body composition were determined using bioimpedance analysis. In the pregnant women, the measurements were conducted in the 16 ± 4th (EP) and 29 ± 4th week of pregnancy (LP) as well as in the 32 ± 9th week postpartum (PP). Muscle thickness and pennation angle of the fascicles significantly increased at LP, while muscle strength remained constant during and after pregnancy. Body mass, skeletal muscle mass, fat mass, intracellular and extracellular water also peaked at LP. Postpartum values did not differ from the controls. Changes in the muscle properties were not related to changes in body mass and body composition. Conditions during pregnancy promote changes in the vastus lateralis architecture indicating muscle hypertrophy. However, pregnancy did not increase muscle strength while body mass progressively increases. Therefore, in the event of balance perturbations pregnant women may not be able to meet the requirements for the increased physical demand.

It is believed that hormonal changes during pregnancy lead to an increased compliance in ligaments and tendons, increasing the risk to suffer from connective tissue injuries particularly during exercise. While the laxity of the pelvic ligaments may increase to facilitate childbirth, to our knowledge no study has ever investigated the mechanical properties of human tendons in different stages of pregnancy. Thus, the purpose of our longitudinal study was to investigate the mechanical properties of the patellar tendon in different stages of pregnancy and postpartum. Nineteen pregnant women (30 ± 4 years) and 11 non-pregnant controls (28 ± 3 years) performed maximum isometric knee extension contractions on a dynamometer. Muscle strength and mechanical properties of the patellar tendon were determined integrating ultrasound, kinematic, and electromyographic measurements. In pregnant women, measurements were performed in the 16 ± 4th week of pregnancy (EP), the 29 ± 4th week of pregnancy (LP) and 32 ± 9th weeks postpartum (PP). On average, muscle strength as well as patellar tendon stiffness, force, and relative strain did not change during pregnancy and did not differ from non-pregnant controls. Tendon length measured at 90° knee flexion continuously increased during and after pregnancy (tendon length PP>EP; PP>controls). Our results indicate that patellar tendon stiffness is not universally affected by pregnancy. We found no evidence to support the often stated assumption that tendons would become more compliant during pregnancy. However, variability between individuals as well as the progressive increase in tendon rest length during and after pregnancy and its implications on injury risk need to be further examined.

The different methods used to assess patellar tendon elongation in vivo may partly explain the large variation of mechanical properties reported in the literature. The present study investigated the effects of tracking landmark position and tibial point of resistive force application during leg extensions in a dynamometer. Nineteen adults performed isometric contractions with a proximal and distal dynamometer shank pad position. Knee joint moments were calculated employing an inverse dynamics approach. Tendon elongation was measured using the patellar apex and either the tibial tuberosity (T) or plateau (P) as tracking landmark. Using P for tracking introduced a bias towards greater values of tendon elongation at all force levels from 100 N to maximum tendon force (TFmax; p

The black-and-white patterning of tendon fascicles when visualized by light microscopy, also known as crimp, is a well-known feature of fiber-forming collagens. However, not much is known about its development, function and response to strain. The objective of this study is to investigate the interaction of tenocyte and crimp morphology as well as their changes with increasing age and acute strain. In contrast to previous studies, which used indirect measures, such as polarized light, to investigate the crimp structure, this study visualizes internal crimp structure in three dimensions without freezing, sectioning, staining or fixing the tissue, via two-photon imaging of green fluorescent protein expressing cells within mouse tail tendon fascicles. This technique further allows straining of the live tissue while visualizing changes in crimp morphology and cell shape with increasing specimen length. Combining this novel microscopy technique with computational image and data analysis revealed a complex relationship between tenocytes and the extracellular matrix that evolves with increasing age. While the reduction of crimping with strain was observed as expected, most of the crimps were gone at 0–1% strain already. Even relatively low strains of 3% led to pronounced changes in the crimp structure after relaxation, particularly in the young animals, which could not be seen with bright-field imaging. Cell length and gap width increased with strain. However, while the cells were able to return to their original length even after high strains of 6%, the gaps between the cells widened, which may imply modified cell–cell communication after overstretching.

Many parents still hesitate to encourage their children to participate in resistance training programs. This is unfortunate since recent research shows that resistance training can positively affect children’s health. This narrative review aims to present an overview of the health-associated effects resistance training can provide particularly in children and adolescents with disabilities by describing its effects on muscle strength, physical function, mental health, self-concept, obesity, and injury prevention. To illustrate the variety of possible fields of application, the effects of resistance training in children and adolescents suffering from Charcot-Marie-Tooth disease, cerebral palsy, Down syndrome, Ehlers-Danlos syndrome, joint hypermobility, juvenile idiopathic arthritis, obesity, and spina bifida are discussed. Although randomized controlled trials with a sufficiently large sample size are rare, the research presented in this review indicates that this mode of training might be a potent tool to improve mental and physical health by improving muscle strength, body composition, self-concept or functionality, reducing pain or injury risk, and strengthening bone or tendons even in the most vulnerable groups of children with physical or mental disability. Furthermore, it has to be emphasized that compared with other types of treatment resistance training is considered to be without adverse effects.

Tendinopathies are a range of diseases characterised by degeneration and chronic tendon pain and represent a significant cause of morbidity. Relatively little is known about the underlying mechanisms; however onset is often associated with physical activity. A number of molecular changes have been documented in tendinopathy such as a decrease in overall collagen content, increased extracellular matrix turnover and protease activity. Metalloproteinases are involved in the homeostasis of the extracellular matrix and expression is regulated by mechanical strain. The aims of this study were to determine the effects of strain upon matrix turnover by measuring metalloproteinase and matrix gene expression and to elucidate the mechanism of action. Primary Human Achilles tenocytes were seeded in type I rat tail collagen gels in a Flexcell™ tissue train system and subjected to 5% cyclic uniaxial strain at 1 Hz for 48 h. TGFβ1 and TGFβRI inhibitor were added to selected cultures. RNA was measured using qRT-PCR and TGFβ protein levels were determined using a cell based luciferase assay. We observed that mechanical strain regulated the mRNA levels of multiple protease and matrix genes anabolically, and this regulation mirrored that seen with TGFβ stimulation alone. We have also demonstrated that the inhibition of the TGFβ signalling pathway abrogated the strain induced changes in mRNA and that TGFβ activation, rather than gene expression, was increased with mechanical strain. We concluded that TGFβ activation plays an important role in mechanotransduction. Targeting this pathway may have its place in the treatment of tendinopathy., Highlights • Mechanical strain regulates multiple protease and matrix genes at the mRNA level. • Changes in mRNA level are analogous to those induced by TGFβ stimulation. • The inhibition of the TGFβ signalling pathway abrogated the strain-induced changes. • A SMAD activatory soluble factor is increased in activity in response to mechanical load.

Cyclic and static loading regimes are commonly used to study tenocyte metabolism in vitro and to improve our understanding of exercise-associated tendon pathologies. The aims of our study were to investigate if cyclic and static stress relaxation affected the mechanical properties of tendon fascicles differently, if this effect was reversible after a recovery period, and if the removal of glycosaminoglycans (GAGs) affected sample recovery. Tendon fascicles were dissected frombovine-foot extensors and subjected to 14% cyclic (1Hz) or static tensile strain for 30min. Additional fascicles were incubated overnight in buffer with 0.5U chondroitinase ABC or in buffer alone prior to the static stress-relaxation regime. To assess the effect of different stress-relaxation regimes, a quasi-static test to failure was carried out, either directly post loading or after a 2h recovery period, and compared with unloaded control fascicles. Both stress-relaxation regimes led to a significant reduction in fascicle failure stress and strain, but this was more pronounced in the cyclically loaded specimens. Removal of GAGs led to more stress relaxation and greater reductions in failure stress after static loading compared to controls. The reduction in mechanical properties was partially reversible in all samples, given a recovery period of 2h. This has implications for mechanical testing protocols, as a time delay between fatiguing specimens and characterization of mechanical properties will affect the results. GAGs appear to protect tendon fascicles from fatigue effects, possibly by enabling sample hydration.

Tendinopathies, chronic tendon disorders characterized by pain and functional impairment, are a common problem particularly in elite and recreational athletes. There is a high prevalence of Achilles tendinopathy in runners, while patellar tendinopathies, also referred to as jumpers knee, are very common amongst volleyball and basketball players. However, tendinopathies also occur in the sedentary population. The syndrome is associated with a variety of morphological, histopathological, biochemical and molecular changes, such as an increase in tendon cross sectional area, loss of fibre organization and infiltration of blood vessels. It has been shown that exercise or mechanical loading plays a role, which is why overuse is suspected to initiate tendinopathies. The exact mechanisms are still poorly understood, which makes the treatment problematic. A variety of treatment options are available, ranging from non-invasive procedures such as exercise treatment, topical nitroglycerin patches or shock wave therapy, over injections of various substances, such as corticosteroids, platelet-rich plasma or sclerosing agents, to surgical debridement. However, most of the treatment options focus solely on symptom relief, and the evidence for their effectiveness is often poor. The effectiveness of a treatment is furthermore likely to depend on the stage of the tendinapathy. In contrast to many therapies, exercise treatment has been relatively well investigated, has been shown to work in the majority of cases and is considered the gold standard.

Repetitive strain or 'overuse' is thought to be a major factor contributing to the development of tendinopathy. The aims of our study were to develop a novel cyclic loading system, and use it to investigate the effect of defined loading conditions on the mechanical properties and gene expression of isolated tendon fascicles. Tendon fascicles were dissected from bovine-foot extensors and subjected to cyclic tensile strain (1 Hz) at 30% or 60% of the strain at failure, for 0 h (control), 15 min, 30 min, 1 h, or 5 h. Post loading, a quasi-static test to failure assessed damage. Gene expression at a selected loading regime (1 h at 30% failure strain) was analyzed 6 h post loading by quantitative real-time polymerase chain reaction. Compared with unloaded controls, loading at 30% failure strain took 5 h to lead to a significant decrease in failure stress, whereas loading to 60% led to a significant reduction after 15 min. Loading for 1 h at 30% failure strain did not create significant structural damage, but increased Collagen-1-alpha-chain-1 and interleukin-6 (IL6) expression, suggesting a role of IL6 in tendon adaptation to exercise. Correlating failure properties with fatigue damage provides a method by which changes in gene expression can be associated with different degrees of fatigue damage.

Summary The aim of this study was to evaluate the suitability of ultrasonography for the quantification of gastrocnemius muscle architecture in healthy young children. The variation and reliability of measurement of muscle thickness, pennation angle and fibre length of the medial gastrocnemius were determined, using stationary and portable ultrasound machines, in 13 boys and eight girls aged 4‐10. Ultrasound images were obtained from each leg, in duplicate, with the ankle at 90� , then at maximal plantar flexion, with the two machines within the same session. The same set of 16 scans was repeated in four children 4‐6 weeks later. The mean muscle thickness, pennation angle and fibre length differed between ankle positions and between legs. Measurements obtained using the two machines established similar values with no significant differences in absolute values and coefficients of variation (CV). For duplicate images taken during the same session for the same leg, ankle position and machine, the CV and intraclass correlation coefficients (ICC) ranged, respectively, from 2AE1% to 3AE1% and 0AE94‐0AE98 for muscle thickness, from 4AE1% to 6AE0% and 0AE85‐0AE96 for pennation angle and from 4AE5% to 6AE3% and 0AE87‐0AE96 for fibre length. Corresponding values for variables for the same child measured on two separate occasions were within the same ranges, all being similar to reliability data reported previously for adult muscle. Muscle thickness, pennation angle and fibre length of the medial gastrocnemius can therefore be quantified reliably, using either a stationary or portable ultrasound machine, in healthy young children.

Introduction It has yet to be explained why female athletes appear to suffer more often from non‐contact ligament injuries during the first half of the menstrual cycle. Fluctuations in balance, caused by impaired proprioception due to increased fluid retention, may be relevant factors contributing to this anomaly in distribution. The aim of this study was therefore to uncover relationships between dynamic stability, proprioception and fluid retention in association with the menstrual cycle as a possible explanation for the observed changes in injury rates. Methods Nine healthy, female, well trained ice hockey players on hormonal contraception with regular cycles were tested at least twelve times during one menstrual cycle. Bioimpedance analysis was applied to investigate body composition and fluid distribution. A joint position sense test was performed to characterize changes in proprioception, while unexpected perturbations on a balance board were used to obtain measures for dynamic postural control. Results No distinct changes in proprioception, dynamic stability and fluid retention were identified across the menstrual cycle in this population. Weak correlations were found between parameters for dynamic stability and proprioception. Conclusion Variations in proprioception, dynamic stability and fluid retention seem unlikely to be major contributors to injury risk peaks, at least in this population of healthy trained athletes using hormonal contraception.

Intramuscular injections of the paralytic botulinum neurotoxin A (Btx) and physical exercise are used in the treatment of chronic spasticity in children with cerebral palsy. We tested whether Btx-induced paralysis and/or exercise training would have differential effects on the expression of mechanosensing and signalling genes implicated in the adaptive remodelling of skeletal muscle. Juvenile (29-day-old) male rats were injected with Btx or saline (NoBtx) into the right gastrocnemius and housed in standard cages (NoEx) or with running wheels (Ex), for 3 weeks (n = 6 per group). The mRNA expression of nine sarcomere-associated genes in the medial gastrocnemius was then determined by quantitative reverse transcriptase-polymerase chain reaction. The Btx-injected muscles weighed 50% less than NoBtx muscles, but Ex had no effect on the wet mass of Btx or NoBtx muscles. Atrogenic MuRF1, sarcomeric Titin and myogenic MyoD were upregulated (2-fold) with the elimination of contractile activity in Btx muscle. Expression of CARP, Ankrd2 and MLP was increased with mechanical stimuli associated with Btx (5- to 10-fold) or Ex (2- to 4-fold). Expression of CARP and Ankrd2 increased synergistically in Btx-Ex muscle (> or = 20-fold), indicating that these genes may be sensitive to passive stretch of the sarcomeric I-band region of titin to which their proteins bind. Tcap, Myopalladin and Atrogin1 were not, or were no longer responsive to the altered mechanical stimuli after 3 weeks of Btx or Ex. The expression of Ankrd2, CARP and MLP may thus be enhanced by passive stretch within the Btx-paralysed and/or exercising gastrocnemius and contribute to adaptations, other than muscle mass, in juvenile rats.

The myogenic regulatory factor MyoD plays an important role in embryonic and adult skeletal muscle growth. Even though it is best known as a marker for activated satellite cells, it is also expressed in myonuclei, and its expression can be induced by a variety of different conditions. Several model systems have been used to study the mechanisms behind MyoD regulation, such as exercise, stretch, disuse, and denervation. Since MyoD reacts in a highly muscle-specific manner, and its expression varies over time and between species, universally valid predictions and explanations for changes in MyoD expression are not possible. This review explores the complex role of MyoD in muscle plasticity by evaluating the induction of MyoD expression in the context of muscle composition and electrical and mechanical stimulation.

The aims of this study were to characterize the pattern of voluntary activity of young rats in response to resistance loading on running wheels and to determine the effects of the activity on the growth of six limb skeletal muscles. Male Sprague–Dawley rats (4 weeks old) were housed individually with a resistance running wheel (R-RUN, n= 7) or a conventional free-spinning running wheel (F-RUN, n= 6) or without a wheel, as non-running control animals (CON, n= 6). The torque required to move the wheel in the R-RUN group was progressively increased, and the activity (velocity, distance and duration of each bout) of the two running wheel groups was recorded continuously for 45 days. The R-RUN group performed many more, shorter and faster bouts of running than the F-RUN group, yet the mean daily distance was not different between the F-RUN (1.3 ± 0.2 km) and R-RUN group (1.4 ± 0.6 km). Only the R-RUN resulted in a significantly (P < 0.05) enhanced muscle wet mass, relative to the increase in body mass, of the plantaris (23%) and vastus lateralis muscle (17%), and the plantaris muscle fibre cross-sectional area, compared with CON. Both F-RUN and R-RUN led to a significantly greater wet mass relative to increase in body mass and muscle fibre cross-sectional area in the soleus muscle compared with CON. We conclude that the pattern of voluntary activity on a resistance running wheel differs from that on a free-spinning running wheel and provides a suitable model to induce physiological muscle hypertrophy in rats.

Compared with muscle or bone, there is a lack of information about the relationship between tendon adaptation and the applied loading characteristic. The purpose of the present study was to analyze the effect of different exercise modes characterized by very distinct loading patterns on the mechanical, morphological, and biochemical properties of the Achilles tendon. Sixty-four female Sprague-Dawley rats were divided into five groups: nonactive age-matched control (AMC; n = 20), voluntary wheel running (RT; n = 20), vibration strength-trained (LVST; n = 12), high-vibration strength-trained (HVST; n = 6), and high strength-trained (HST; n = 6) group. After a 12-wk-long experimental period, the Achilles tendon was tested mechanically and the cross-sectional area, the soleus and gastrocnemius muscle mass, and mRNA concentration of collagen I, collagen III, tissue inhibitor of metalloproteinase-1 (TIMP-1), transforming growth factor-β, connective tissue growth factor, and matrix metalloproteinase-2 was determined. Neither in the LVST nor in the HVST group could any adaptation of the Achilles tendon be detected, although the training had an effect on the gastrocnemius muscle mass in the LVST group ( P < 0.05). In the HST group, the highest creep was found, but the effect was more pronounced compared with the LVST group ( P < 0.05) than with the AMC group. That indicates that this was rather induced by the low muscle mass rather than by training. However, the RT group had a higher TIMP-1 mRNA concentration in the Achilles tendon in contrast to AMC group ( P < 0.05), which suggests that this exercise mode may have an influence on tendon adaptation.

Most overuse tendinopathies are thought to be associated with repeated microstrain below the failure threshold, analogous to the fatigue failure that affects materials placed under repetitive loading. Investigating the progression of fatigue damage within tendons is therefore of critical importance. There are obvious challenges associated with the sourcing of human tendon samples for in vitro analysis so animal models are regularly adopted. However, data indicates that fatigue life varies significantly between tendons of different species and with different stresses in life. Positional tendons such as rat tail tendon or the bovine digital extensor are commonly applied in in vitro studies of tendon overuse, but there is no evidence to suggest their behaviour is indicative of the types of human tendon particularly prone to overuse injuries. In this study, the fatigue response of the largely positional digital extensor and the more energy storing deep digital flexor tendon of the bovine hoof were compared to the semitendinosus tendon of the human hamstring. Fascicles from each tendon type were subjected to either stress or strain controlled fatigue loading (cyclic creep or cyclic stress relaxation respectively). Gross fascicle mechanics were monitored after cyclic stress relaxation and the mean number of cycles to failure investigated with creep loading. Bovine extensor fascicles demonstrated the poorest fatigue response, while the energy storing human semitendinosus was the most fatigue resistant. Despite the superior fatigue response of the energy storing tendons, confocal imaging suggested a similar degree of damage in all three tendon types; it appears the more energy storing tendons are better able to withstand damage without detriment to mechanics.

Overuse tendinopathies are often considered to be the result of repeated microstrain below the failure threshold, analogous to the fatigue failure of materials under repeated loading [1, 2]. Investigation of tendon overuse in vitro is thus of potential benefit towards characterizing the progression of damage.

Objectives. Histological examination of pathological tendon generally does not reveal signs of inflammation. However, the inflammatory cytokine IL-6 has been shown to be expressed in ruptured rotator cuff tendon. The aim of this study was to investigate the expression of IL-6 family members in painful posterior tibialis tendon (PTT) and in painful and ruptured Achilles tendon (AT) compared with normal tendon. Methods. AT samples were obtained from cadavers (normal) or from patients undergoing surgical procedures to treat chronic painful tendinopathy or ruptured tendon. PTT samples were obtained from patients undergoing surgery for other reasons (normal) and from patients with PTT dysfunction (painful). Total RNA was extracted and mRNA expression was analysed by quantitative real-time PCR. Results. Collagen type I α-chain I (COL1A1) expression was increased in both painful PTT and AT compared with normal. Ciliary neurotrophic factor levels were increased in painful PTT only. In the painful AT, cyclooxygenase-2 (COX2) and IL-6 expression increased compared with normal. In the ruptured AT, levels of VEGF A, COX2, oncostatin-M, leukaemia inhibitory factor and IL-6 expression were higher compared with both normal and painful AT. IL-6R expression decreased in both painful and ruptured AT compared with normal. Conclusion. Painful AT and PTT show different expression patterns, indicating a substantial difference between those two tendinopathies. Inflammatory markers are up-regulated in painful and particularly in ruptured AT, pointing towards a role of inflammation not only in rupture healing, but also in Achilles tendinopathy.

Stress, strain and modulus are regularly used to characterize material properties of tissue samples. However, when comparing results from different studies it is evident the reported material properties, particularly failure strains, vary hugely. The aim of our study was to characterize how and why specimen length and cross-sectional area (CSA) appear to influence failure stress, strain and modulus in fascicles from two functionally different tendons. Fascicles were dissected from five rat tails and five bovine foot extensors, their diameters determined by a laser micrometer, and loaded to failure at a range of grip-to-grip lengths. Strain to failure significantly decreased with increasing in specimen length in both rat and bovine fascicles, while modulus increased. Specimen length did not influence failure stress in rat tail fascicles, although in bovine fascicles it was significantly lower in the longer 40mm specimens compared to 5 and 10mm specimens. The variations in failure strain and modulus with sample length could be predominantly explained by end-effects. However, it was also evident that strain fields along the sample length were highly variable and notably larger towards the ends of the sample than the mid-section even at distances in excess of 5mm from the gripping points. Failure strain, stress and modulus correlated significantly with CSA at certain specimen lengths. Our findings have implications for the mechanical testing of tendon tissue: while it is not always possible to control for fascicle length and/or CSA, these parameters have to be taken into account when comparing samples of different dimensions.

Intramuscular injections of botulinum toxin A (Btx-A) and exercise are used in the treatment of muscle spasticity in children with cerebral palsy. However, little is known about the biological changes within muscle subsequent to Btx-A-induced paralysis and how the combination of Btx-A and exercise might affect the growing muscle. The wet mass, myosin heavy chain (MHC) composition, and titin content of the juvenile rat gastrocnemius muscle were determined 3 weeks after Btx-A injections and subsequent voluntary wheel-running exercise. Btx-A increased the proportion of type IIa (+121%) and IIx (+65%) MHC while decreasing the proportion of type IIb MHC (−51%) and reducing the titin content (−18%). Exercise did not amplify or reduce the changes induced by Btx-A. Thus, we conclude that although the sarcomeric stability of paralyzed muscle might be impaired, moderate mechanical loading does not seem to affect paralyzed muscle protein composition. Muscle Nerve, 2008

Intramuscular injections of the paralytic botulinum neurotoxin A (Btx) and physical exercise are used in the treatment of chronic spasticity in children with cerebral palsy. We tested whether Btx-induced paralysis and/or exercise training would have differential effects on the expression of mechanosensing and signalling genes implicated in the adaptive remodelling of skeletal muscle. Juvenile (29-day-old) male rats were injected with Btx or saline (NoBtx) into the right gastrocnemius and housed in standard cages (NoEx) or with running wheels (Ex), for 3 weeks (n = 6 per group). The mRNA expression of nine sarcomere-associated genes in the medial gastrocnemius was then determined by quantitative reverse transcriptase-polymerase chain reaction. The Btx-injected muscles weighed 50% less than NoBtx muscles, but Ex had no effect on the wet mass of Btx or NoBtx muscles. Atrogenic MuRF1, sarcomeric Titin and myogenic MyoD were upregulated (2-fold) with the elimination of contractile activity in Btx muscle. Expression of CARP, Ankrd2 and MLP was increased with mechanical stimuli associated with Btx (5- to 10-fold) or Ex (2- to 4-fold). Expression of CARP and Ankrd2 increased synergistically in Btx-Ex muscle (or = 20-fold), indicating that these genes may be sensitive to passive stretch of the sarcomeric I-band region of titin to which their proteins bind. Tcap, Myopalladin and Atrogin1 were not, or were no longer responsive to the altered mechanical stimuli after 3 weeks of Btx or Ex. The expression of Ankrd2, CARP and MLP may thus be enhanced by passive stretch within the Btx-paralysed and/or exercising gastrocnemius and contribute to adaptations, other than muscle mass, in juvenile rats.

The aims of this study were to characterize the pattern of voluntary activity of young rats in response to resistance loading on running wheels and to determine the effects of the activity on the growth of six limb skeletal muscles. Male Sprague-Dawley rats (4 weeks old) were housed individually with a resistance running wheel (R-RUN, n = 7) or a conventional free-spinning running wheel (F-RUN, n = 6) or without a wheel, as non-running control animals (CON, n = 6). The torque required to move the wheel in the R-RUN group was progressively increased, and the activity (velocity, distance and duration of each bout) of the two running wheel groups was recorded continuously for 45 days. The R-RUN group performed many more, shorter and faster bouts of running than the F-RUN group, yet the mean daily distance was not different between the F-RUN (1.3 +/- 0.2 km) and R-RUN group (1.4 +/- 0.6 km). Only the R-RUN resulted in a significantly (P0.05) enhanced muscle wet mass, relative to the increase in body mass, of the plantaris (23%) and vastus lateralis muscle (17%), and the plantaris muscle fibre cross-sectional area, compared with CON. Both F-RUN and R-RUN led to a significantly greater wet mass relative to increase in body mass and muscle fibre cross-sectional area in the soleus muscle compared with CON. We conclude that the pattern of voluntary activity on a resistance running wheel differs from that on a free-spinning running wheel and provides a suitable model to induce physiological muscle hypertrophy in rats.