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Publications
Publications (707)
Knowledge of how to treat chronic tendinopathy has advanced in recent years, but the treatment of early tendinopathy is not well understood. The main purpose of this prospective observational study was to investigate if changes occur in clinical and imaging outcomes over 12 weeks in elite athletes with recent debut of tendinopathy. Sixty‐five elite...
A major challenge in sports medicine is to facilitate the fastest possible recovery from injury without increasing the risk of subsequent reruptures, and thus effective rehabilitation programs should balance between these two factors. The present review focuses on examining the role of different resistance training interventions in rehabilitation o...
Exercise preserves neuromuscular function in ageing through unknown mechanisms. Skeletal muscle fibroblasts (FIB) and stem cells (MuSC) are abundant in skeletal muscle and reside close to neuromuscular junctions, but their relative roles in motor neuron maintenance remain undescribed. Using direct co-cultures of embryonic rat motor neurons with eit...
Prematurity has physical consequences, such as lower birth weight, decreased muscle mass and increased risk of adult‐onset metabolic disease. Insulin‐like growth factor 1 (IGF‐1) has therapeutic potential to improve the growth and quality of muscle and tendon in premature births, and thus attenuate some of these sequalae. We investigated the effect...
Objectives
Muscle function and size decline with age, but long-term effects of resistance training in older adults are largely unknown. Here, we explored the long-lasting (3 years) effects of 1 year of supervised resistance training with heavy loads.
Methods
The LIve active Successful Ageing (LISA) study was a parallel group randomised controlled...
The musculoskeletal system, crucial for movement and support, relies on the delicate balance of connective tissue homeostasis. Maintaining this equilibrium is essential for tissue health and function. There has been increasing evidence in the last decade that shows the circadian clock as a master regulator of extracellular matrix (ECM) homeostasis...
INTRODUCTION
Patients with diabetes have an increased risk of developing tendon injuries, which may be due to prolonged weakening of connective tissue caused by metabolic imbalance. We investigated whether the current standard care for type 2 diabetes, which reduces blood sugar and lipid levels, also reduces the risk of tendon injuries. This had no...
Physical activity can activate extracellular matrix (ECM) protein synthesis and influence the size and mechanical properties of tendon. In this study, we aimed to investigate whether different training histories of horses would influence the synthesis of collagen and other matrix proteins and alter the mechanical properties of tendon. Samples from...
Background
Plantar fasciitis is a painful tendinous condition (tendinopathy) with a high prevalence in athletes. While a healthy tendon has limited blood flow, ultrasound has indicated elevated blood flow in tendinopathy, but it is unknown if this is related to a de facto increase in the tendon vasculature. Likewise, an accumulation of glycosaminog...
The myotendinous junction (MTJ) is a weak link in the musculoskeletal system. Here, we isolated the tips of single myofibres from healthy human hamstring muscles for confocal microscopy (n=6) and RNAscope in situ hybridization (n=6) to gain insight into the profiles of cells and myonuclei in this region. A marked presence of mononuclear cells was o...
Background
Achilles tendon ruptures often result in long-term functional deficits despite accelerated (standard) rehabilitation.
Purpose/Hypothesis
The purpose of this study was to investigate if delayed loading would influence functional, clinical, and structural outcomes of the muscles and tendon 1 year after a surgical repair. It was hypothesiz...
Muscle inactivity may reduce basal and postprandial muscle protein synthesis (MPS) rates in humans. Anti‐inflammatory treatment alleviates the MPS impairments in younger individuals. The present study explored the influence of nonsteroidal anti‐inflammatory drugs (NSAIDs) upon MPS during a period of inactivity in older humans. Eighteen men (age 60–...
Background
Modifiable risk factors have been shown to promote healthy brain ageing. However, most studies to date have focused on the relationship between a single risk factor and brain health. Given that risk factors do not occur in isolation, multivariable analyses may provide a more realistic model of the effects of modifiable lifestyle factors...
Background
Age‐related loss of strength is disproportionally greater than the loss of mass, suggesting maladaptations in the neuro‐myo‐tendinous system. Myofibers are often misshaped in aged and diseased muscle, but systematic analyses of large sample sets are lacking. Our aim was to investigate myofiber shape in relation to age, exercise, myofiber...
Physical activity (PA) promotes brain health in a variety of domains including cognition, mood, and neuroplasticity. At the neurochemical level, the mechanisms underlying these effects in the brain are not fully understood. With proton Magnetic Resonance Spectroscopy (¹H-MRS), it is possible to non-invasively quantify metabolite concentrations, ena...
Background:
Muscle strain injuries in the human calf muscles are frequent sports injuries with high recurrence. Potential structural and functional changes in the medial head of the musculus gastrocnemius (GM) and the associated aponeurosis are not well documented.
Purpose:
To test whether a GM muscle strain injury affects muscle fascicle length...
Background
The occurrence of hyperplasia, through myofibre splitting, remains a widely debated phenomenon. Structural alterations and fibre typing of skeletal muscle fibres, as seen during regeneration and in certain muscle diseases, can be challenging to interpret. Neuromuscular electrical stimulation can induce myofibre necrosis followed by chang...
Modifiable lifestyle factors have been shown to promote healthy brain ageing. However, studies have typically focused on a single factor at a time. Given that lifestyle factors do not occur in isolation, multivariable analyses provide a more realistic model of the lifestyle-brain relationship. Here, canonical correlation analyses (CCA) examined the...
Background:
Permanent loss of muscle function seen after an Achilles tendon rupture may partly be explained by tendon elongation and accompanying shortening of the muscle.
Hypothesis:
Muscle fascicle length shortens, serial sarcomere number is reduced, and the sarcomere length is unchanged after Achilles tendon transection (ATT) and these change...
Background
Age-related loss of strength is disproportionally greater than the loss of mass, suggesting maladaptations in the neuro-myo-tendinous system. Myofibers are often misshaped in aged and diseased muscle, but systematic analyses of large sample sets are lacking. Our aim was to investigate myofiber shape in relation to age, exercise, myofiber...
Background: The occurrence of hyperplasia, through myofibre splitting, remains a widely debated phenomenon. Structural alterations and fibre typing of skeletal muscle fibres, as seen during regeneration and in certain muscle diseases, can be challenging to interpret. Neuromuscular electrical stimulation can induce myofibre necrosis followed by chan...
Understanding individual variability in response to physical activity is key to developing more effective and personalised interventions for healthy ageing. Here, we aimed to unpack individual differences by using longitudinal data from a randomised-controlled trial of a 12-month muscle strengthening intervention in older adults. Physical function...
The myotendinous junction (MTJ) is a specialized domain of the multinucleated myofibre, faced with the challenge of maintaining robust cell-matrix contact with the tendon under high mechanical stress and strain. Here, we profiled 24,161 nuclei in semitendinosus muscle-tendon samples from 3 healthy males by single nucleus RNA-sequencing (snRNA-seq),...
Overuse injury in tendon tissue (tendinopathy) is a frequent and costly musculoskeletal disorder and represents a major clinical problem with unsolved pathogenesis. Studies in mice have demonstrated that circadian clock-controlled genes are vital for protein homeostasis and important in the development of tendinopathy. We performed RNA sequencing,...
Objective:
Osteoarthritis (OA) remains clinically challenging. Regular physical exercise improves symptoms though it is unclear whether exercise influences cartilage at the molecular level. Thus, we aimed to determine the effect of acute loading on gene expression and glycosaminoglycan (GAG) content in human OA cartilage.
Design:
Patients with p...
Introduction
The optimal rehabilitation following Achilles tendon rupture is still missing. It has been suggested that preventing tendon elongation during rehabilitation improves the clinical outcome, which leads to the purpose of this study; investigating if delayed loading following surgical treated Achilles tendon rupture influences the clinical...
Skeletal muscle possesses adaptability to mechanical loading and regenerative potential following muscle injury due to muscle stem cell activity. So far, it is known that muscle stem cell activity is supported by the roles of several interstitial cells within skeletal muscle in response to muscle damage. The adjacent tendon is also exposed to repet...
Purpose/Aim of the study
Osteogenesis imperfecta is a heritable bone disorder that is usually caused by mutations in collagen type I encoding genes. The impact of such mutations on tendons, a structure with high collagen type I content, remains largely unexplored. We hypothesized that tendon properties are abnormal in the context of a mutation affe...
The myotendinous junction (MTJ) is a specialized domain of the multinucleated myofibre, faced with the challenge of maintaining robust cell-matrix contact with the tendon under high mechanical stress and strain. Here, we profiled 24,161 nuclei in semitendinosus muscle-tendon samples from 3 healthy males by single nucleus RNA-sequencing (snRNA-seq),...
Objectives:
This study investigated the effect of lower limb immobilization and retraining on postural control and muscle power in healthy old and young men.
Methods:
Twenty men, nine old (OM:67.3±4.4 years) and eleven young (YM:24.4±1.6 years) underwent 2 weeks of unilateral whole-leg casting, followed by 4 weeks of retraining. Measures include...
The myotendinous junction (MTJ) is structurally specialized to transmit force. The highly folded muscle membrane at the MTJ increases the contact area between muscle and tendon and potentially the load tolerance of the MTJ. Muscles with a high content of type II fibers are more often subject to strain injury compared to muscles with type I fibers....
Increasing age appears to influence several morphologic changes in major tendons. However, the effects of aging on the cross-sectional area (CSA) of different ankle tendons are much less understood. Furthermore, potential differences in specific tendon regions along the length of the tendons have not been investigated in detail. Sixty healthy adult...
The present pilot study investigated the extent of histological tissue changes in both chronic tendinopathy and in individuals that display early clinical signs of tendinopathy. The study included 8 individuals of whom 3 were healthy without any tendon symptoms, 2 had early symptoms (1–2 months), and 3 had chronic symptoms (>3 months) from their pa...
Background
Lateral elbow tendinopathy is a disabling tendon overuse injury. It remains unknown if a corticosteroid injection (CSI) or tendon needling (TN) combined with heavy slow resistance (HSR) training is superior to HSR alone in treating lateral elbow tendinopathy.
Purpose/Hypothesis
The purpose was to investigate the effects of HSR combined...
Persistent muscle weakness, tendon elongation, and incomplete return to preinjury level are frequent sequelae after acute Achilles tendon rupture, and evidence-based knowledge of how to best rehabilitate the injury is largely absent in the literature. The objective of this review is to illuminate and discuss to what extent an Achilles tendon ruptur...
The myotendinous junction (MTJ), a specialized interface for force transmission between muscle and tendon, has a unique transcriptional activity and is highly susceptible to muscle strain injury. Eccentric exercise training is known to reduce this risk of injury, but knowledge of the influence of exercise on the MTJ at the molecular and cellular le...
Aging is accompanied by morphological and mechanical changes to the intramuscular connective tissue (IMCT) of skeletal muscles, but whether physical exercise can influence these changes is debated. We investigated the effects of aging and exercise with high or low resistance on composition and mechanical properties of the IMCT, including direct mea...
Muscle fiber denervation is a major contributor to the decline in muscle mass and function during aging. Heavy resistance exercise is an effective tool for increasing muscle mass and strength, but whether it can rescue denervated muscle fibers remains unclear. Therefore, the purpose of this study was to investigate the potential of heavy resistance...
Skeletal muscle possesses remarkable adaptability to mechanical loading and regenerative potential following muscle injury primarily due to satellite cell activity. Although the roles of several types of interstitial cells in skeletal muscle have been documented, the signaling interplay between the skeletal muscle and the adjacent tendon tissue has...
The circadian clock controls many aspects of physiology, but it remains undescribed whether extracellular vesicles (EVs), including exosomes, involved in cell-cell communications between tissues are regulated in a circadian pattern. We demonstrate a 24-hour rhythmic abundance of individual proteins in small EVs using liquid chromatography-mass spec...
Tendons are vital collagen-dense specialized connective tissues transducing the force from skeletal muscle to the bone, thus enabling movement of the human body. Tendon cells adjust matrix turnover in response to physiological tissue loading and pathological overloading (tendinopathy). Nevertheless, the regulation of tendon matrix quality control i...
Muscle fibre denervation and declining numbers of muscle stem (satellite) cells are defining characteristics of ageing skeletal muscle. The aim of this study was to investigate the potential for lifelong recreational exercise to offset muscle fibre denervation and compromised satellite cell content and function, both at rest and under challenged co...
Objective
Cartilage collagen has very limited repair potential, though some turnover and incorporation has not been fully excluded. We aim to determine the regional turnover of human osteoarthritis cartilage.
Design
Patients scheduled for knee joint replacement surgery due to osteoarthritis were recruited in this prospective study of four weeks du...
Proteomics analysis of skeletal muscle has recently progressed from whole muscle tissue to single myofibers. Here, we further focus on a specific myofiber domain crucial for force transmission from muscle to tendon, the myotendinous junction (MTJ). To overcome the anatomical constraints preventing the isolation of pure MTJs, we performed in-depth a...
Introduction
The myotendinous junction (MTJ) has a unique transcriptional activity and is highly susceptible to strain injury. Eccentric exercise reduces this risk of injury, but the mechanism is unknown. The aim of this study was to investigate the effect of a single bout of eccentric exercise on the expression levels of some of the genes known to...
Background
Resistance training is an effective strategy to counteract the age-related loss of muscle mass and -strength in elderly, but whether the benefits of training differ between sexes is unclear.
Method
297 elderly men and women were randomized to one year of heavy resistance training (HRT) or control (CON). Changes in muscle function and bo...
Insight into the bidirectional signaling between primary human myogenic cells and neurons is lacking. For this purpose, human myogenic cells were derived from the semitendinosus and gracilis muscles of five healthy individuals and co‐cultured with cerebellar granule neurons from two litters of 7‐day‐old Wistar rat pups, in muscle medium or neural m...
Physical exercise results in a duration and intensity dependent vascular response in healthy human tendon. In overused (tendinopathy) and damaged tendon, angiogenic pathways are activated and neovascularization is observed. Whereas no direct relationship exists between the amount of neo‐vessels and degree of tendinopathy symptoms, almost all tendin...
Tendons are connective tissues that transmit mechanical forces from muscle to bone and consist mainly of nano-scale fibrils of type I collagen. Aging has been associated with reduced mechanical function of tendons at the whole-tendon level and also with increased glycation of tendon collagen fibrils. Yet, the mechanical effects of aging at the fibr...
Effects of life-long physical activity on tendon function have been investigated in cross-sectional studies, but these are at risk of "survivorship" bias. Here, we investigate if life-long side-specific loading is associated with greater cross-sectional area (CSA), mechanical properties, cell density (DNA content) and collagen cross-link compositio...
Background
Muscle strain injury leads to a high risk of recurrent injury in sports and can cause long-term symptoms such as weakness and pain. Scar tissue formation after strain injuries has been described, yet what ultrastructural changes might occur in the chronic phase of this injury have not. It is also unknown if persistent symptoms and morpho...
Loading intervention is currently the preferred management of tendinopathy, but to what extent different loading regimes influence the mechanical response in tendons is scarcely investigated. Therefore, the purposes of the investigation were to examine the effect of exercise interventions with either high or low load magnitude applied to the tendin...
The myotendinous junction (MTJ) is a specialised interface for transmitting high forces between muscle and tendon and yet the MTJ is a common site of strain injury with a high recurrence rate. The aim of this study was to identify previously unknown MTJ components in mature animals and humans. Samples were obtained from the superficial digital flex...
It is well known that cells can generate endogenous forces onto the extracellular matrix, but to what extent the mechanical properties of the matrix influences these endogenous cellular forces remains unclear. We therefore sought to quantify the influence of matrix rigidity on cell-matrix interactions by inducing cross-links using increasing concen...
Ageing leads to a decline in white matter microstructure and dexterous function of the hand. In adolescents, it has previously been shown that the degree of right-left asymmetry in the corticospinal tract (CST) is linearly related with right-left asymmetry in dexterity. Here, we tested whether this association is also expressed in older adults. Par...
Background
Heavy slow resistance (HSR) training is currently recommended as part of the treatment of patellar tendon tendinopathy. However, treatment success is not reached in all patients, and combinations of different treatments could be beneficial. Local administration of insulin-like growth factor-1 (IGF-1) in humans has been shown to quickly s...
Tendon injury is a considerable problem affecting both physically active and sedentary people. The aim of this study was to examine the relationship between markers for metabolic disorders (hyperglycemia, hypercholesterolemia and metabolic syndrome) and the risk of developing tendon injuries requiring referral to a hospital. The Copenhagen City Hea...
Background: It is believed that clinical management of osteoarthritis should address muscle weakness to improve physical function and prevent disability and frailty.Objectives: This sub-study investigated the effects of supervised progressive resistance training (RT), supervised Nordic Walking (NW), and unsupervised home-based exercise (HBE) on mus...
Background:
Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used in the treatment of Achilles tendinopathy, but whether they have any additive clinical effect on physical rehabilitation in the early phase of tendinopathy remains unknown.
Purpose/hypothesis:
To investigate whether an initial short-term NSAID treatment added to a physic...
Background
T2* mapping has proven useful in tendon research and may have the ability to detect subtle changes at an early stage of tendinopathy.
Purpose
To investigate the difference in T2* between patients with early tendinopathy and healthy controls, and to investigate the relationship between T2* and clinical outcomes, tendon size, and mechanic...
Background
Loading interventions have become a predominant treatment strategy for tendinopathy, and positive clinical outcomes and tendon tissue responses may depend on the exercise dose and load magnitude.
Purpose/Hypothesis
The purpose was to investigate if the load magnitude influenced the effect of a 12-week loading intervention for patellar t...
Objective
Age-related loss of muscle mass and function can be attenuated in rodents with life-long voluntary wheel running with moderate resistance. The present study assessed if sarcopenia could be counteracted with ten weeks high intensity training.
Method
Old (22–23 months) and middle-aged (11 months) mice were divided into three physical activ...
Objectives
Primary frozen shoulder (pFS) has three phases that differ in clinical presentation. It is characterized by contracture of the joint capsule. We hypothesized that there is a general upregulation of collagens in pFS, and that this is highest in the first phase of the disease. The aims of this study were to investigate the expression of va...
The presence of adipocytes at the myotendinous junction (MTJ) has not previously been reported in mammals. However, during studies of the MTJ, our group has noticed the presence of adipocytes as a general and surprising phenomenon.
The main aim of this study was to describe and quantify the presence of adipocytes in relation to the MTJ in healthy...
Background
Fibroblasts are the powerhouses responsible for the production and assembly of extracellular matrix (ECM). Their activity needs to be tightly controlled especially within the musculoskeletal system, where changes to ECM composition affect force transmission and mechanical loading that are required for effective movement of the body. Extr...
Objective
During skeletal growth, the articular cartilage expands to maintain its cover of bones in joints, however, it is unclear when and how cartilage grows. We aim to determine the expanding growth pattern and timing across the tibia plateau in human knees.
Design
Six human tibia plateaus (2 healthy, 2 with osteoarthritis, and 2 with posttraum...
Background
The aim of the current study was to examine different features of the rectus abdominis muscle (RA) in patients with and without a midline incisional hernia to characterize the effects of a hernia on abdominal wall skeletal muscle.
Material and methods
RA tissue from patients undergoing surgical repair of a large midline incisional herni...
Tendon is a highly organized, dense connective tissue that has been demonstrated to have very little turnover. In spite of the low turnover, tendon can grow in response to loading, which may take place primarily at the periphery. Tendon injuries and recurrence of injuries are common in both human and animal in sports. It is unclear why some areas o...
Background
Muscle mass, strength and function declines with advancing age. Strength training (ST) improves these parameters in older adults, but the gains often disappear after completion of a short-term intervention. The purpose of the present study was to investigate muscle mass, -strength and -function one year after the completion of a successf...
The current model for repair of damaged tissue includes immune cells, mediating the progression from a pro-inflammatory to an anti-inflammatory environment. How this process changes with aging in human skeletal muscle under conditions of physiological exercise loading remains unclear. To investigate this, 25 elderly males (mean age 70 ± SD 7 years)...
Integrins are important for mechanosensation in tissue and play, together with nutrition, a role in regulating extracellular matrix (ECM) in skeletal muscle and tendon. Integrin receptors are dimers that consist of an α and β subunit and bridge extracellular and intracellular signals. The present study investigates whether the deletion of the integ...