Tendon Function Research Articles

Relationship Between Ex Vivo Tissue Diffusion Tensor Indexes and Material Properties in Posterior Tibialis Tendon

Category:Ankle, tendon imagingIntroduction/Purpose:Posterior tibialis tendon is of clinical importance in the development and progression of acquired flatfoot and other midfoot deformity. The ability to quantitatively evaluate tendon tissue non-invasively would enable assessment of tendon health status and tracking of recovery from injury. Magnetic resonance diffusion tensor imaging (DTI) has been used to examine tendon tissue organization in healing tendon tissue. However, the relationship of DTI-based measures to tendon mechanical function has not been established. The purpose of this pilot study was to quantitatively evaluate posterior tibialis tendon using DTI and determine the relationship of these parameters to tendon function assessed via ex vivo mechanical testing.Methods:Posterior tibialis tendons from individuals undergoing amputation were positioned vertically in an agarose mold filled with saline for imaging. High resolution diffusion imaging parameters were optimized for tendon on a 3 T MRI to acquire 13 6-mm transverse slices covering the length: 1mm2 isotropic resolution, 2 signal averaging, repetition/echo times of 5000/58 ms, diffusion strength of 500s/mm2 with 30 gradient directions, scan time 5 min. Diffusion images had sufficient quality and were corrected for motion and image distortion. DTI parametric maps including fractional anisotropy (FA), mean, axial, and radial diffusivities (MD, AD, and RD; mm2/s) were calculated along with fiber tracking indexes of fiber length (mm) and density. After imaging, specimens were preloaded to 10 Newtons, preconditioned 10 cycles at 6% strain, subjected to stress-relaxation at 6% strain (10 minutes), then loaded to a maximum of 10% strain. Relationships between DTI indexes and mechanical properties (stiffness and hysteresis) were evaluated using Spearman correlation.Results:Six individuals (4 male, mean(SD) age: 56(5)years, body mass index: 30(6) kg/m2) were included. Reason for amputation was diabetes-related complications in 5 participants and failed orthopaedic surgery in 1 participant. In DTI (Figure 1A), tendons had a tract length of 11.5(11.3)mm and tract density of 23.9(2.4) per ROI. FA, MD, AD, and RD quantify how freely a water molecule is able to move within the tissue, and the directionality of that movement. Tendons had an FA of 0.26(0.25), MD of 1.25(1.28), AD of 1.54(1.57), and RD of 1.11(1.14). Tract length was positively related to linear stiffness (rho=0.829, p=0.04) and hysteresis at 10% strain (rho=0.886, p=0.019) (Figure 1B-D). AD was positively related to hysteresis at 10% strain (rho=0.812, p=0.05).Conclusion:This is the first study to describe posterior tibialis tendon appearance on DTI. Tract length and AD are both related to tendon mechanics. Tract length is based on quantity and directionality of water displacement and may indicate degree of collagen organization given its relationship to stiffness. Tract length and AD related positively to hysteresis, which will require additional research to identify the mechanisms behind this relationship. This study is limited by sample size and specimens that likely do not represent healthy tissue. Regardless, these findings support continued investigation into in vivo imaging of tendon with DTI for quantitative tendon assessment.

Aspirin inhibits adipogenesis of tendon stem cells and lipids accumulation in rat injury tendon through regulating PTEN/PI3K/AKT signalling.

Tendon injury repairs are big challenges in sports medicine, and fatty infiltration after tendon injury is very common and hampers tendon injury healing process. Tendon stem cells (TSCs), as precursors of tendon cells, have shown promising effect on injury tendon repair for their tenogenesis and tendon extracellular matrix formation. Adipocytes and lipids accumulation is a landmark event in pathological process of tendon injury, and this may induce tendon rupture in clinical practice. Based on this, it is important to inhibit TSCs adipogenesis and lipids infiltration to restore structure and function of injury tendon. Aspirin, as the representative of non‐steroidal anti‐inflammatory drugs (NSAIDs), has been widely used in tendon injury for its anti‐inflammatory and analgesic actions, but effect of aspirin on TSCs adipogenesis and fatty infiltration is still unclear. Under adipogenesis conditions, TSCs were treated with concentration gradient of aspirin. Oil red O staining was performed to observe changes of lipids accumulation. Next, we used RNA sequencing to compare profile changes of gene expression between induction group and aspirin‐treated group. Then, we verified the effect of filtrated signalling on TSCs adipogenesis. At last, we established rat tendon injury model and compared changes of biomechanical properties after aspirin treatment. The results showed that aspirin decreased lipids accumulation in injury tendon and inhibited TSCs adipogenesis. RNA sequencing filtrated PTEN/PI3K/AKT signalling as our target. After adding the signalling activators of VO‐Ohpic and IGF‐1, inhibited adipogenesis of TSCs was reversed. Still, aspirin promoted maximum loading, ultimate stress and breaking elongation of injury tendon. In conclusion, by down‐regulating PTEN/PI3K/AKT signalling, aspirin inhibited adipogenesis of TSCs and fatty infiltration in injury tendon, promoted biomechanical properties and decreased rupture risk of injury tendon. All these provided new therapeutic potential and medicine evidence of aspirin in treating tendon injury and tendinopathy.

Tendon stem/progenitor cell ageing: Modulation and rejuvenation.

Tendon ageing is a complicated process caused by multifaceted pathways and ageing plays a critical role in the occurrence and severity of tendon injury. The role of tendon stem/progenitor cells (TSPCs) in tendon maintenance and regeneration has received increasing attention in recent years. The decreased capacity of TSPCs in seniors contributes to impaired tendon functions and raises questions as to what extent these cells either affect, or cause ageing, and whether these age-related cellular alterations are caused by intrinsic factors or the cellular environment. In this review, recent discoveries concerning the biological characteristics of TSPCs and age-related changes in TSPCs, including the effects of cellular epigenetic alterations and the mechanisms involved in the ageing process, are analyzed. During the ageing process, TSPCs ageing might occur as a natural part of the tendon ageing, but could also result from decreased levels of growth factor, hormone deficits and changes in other related factors. Here, we discuss methods that might induce the rejuvenation of TSPC functions that are impaired during ageing, including moderate exercise, cell extracellular matrix condition, growth factors and hormones; these methods aim to rejuvenate the features of youthfulness with the ultimate goal of improving human health during ageing.

Insulin-like growth factor binding protein (IGFBP6) is a cross-species tendon marker.

The main challenge in tendon injury management is suboptimal tissue healing that fails to re-establish original tendon function. Tissue bioengineering is a promising approach for tendon therapy, with potential to improve its functional outcomes. However, evaluation criteria for tissue-engineered tendon are unclear due to the lack of specific markers of differentiated tendon. The study aim was to identify a panel of genes that characterised tendons in comparison to cartilage or muscles and validate those genes, both in human and key species used as models for tendon diseases. Gene expression profiling of rat tendon and cartilage in whole-tissue samples and primary tenocytes and chondrocytes was undertaken using two independent microarray platforms. Genes that demonstrated high expression correlation across two assays were validated by qRT-PCR in rat tendon relative to cartilage and muscle. Five genes demonstrating the highest tendon-related expression in the validation experiment (ASPN, ECM1, IGFBP6, TNMD, THBS4) were further evaluated by qRT-PCR in ovine, equine and human tissue. The group of tendon markers, identified by unbiased transcriptomic analysis of rat musculoskeletal tissues, demonstrated species-dependent profiles of expression. Insulin-like growth factor binding protein 6 (IGFBP6) was identified as the only universal tendon marker. Further investigation in equine tendon showed that IGFBP6 expression was not affected by ageing or tendon function but decreased in anatomical regions subjected to elevated compressive force. IGFBP6 is a robust cross-species marker of tendon phenotype and may find application in evaluation of tendon physiology and guided differentiation of permissive cells towards functional tenocytes.

3D computational models explain muscle activation patterns and energetic functions of internal structures in fish swimming

How muscles are used is a key to understanding the internal driving of fish swimming. However, the underlying mechanisms of some features of the muscle activation patterns and their differential appearance in different species are still obscure. In this study, we explain the muscle activation patterns by using 3D computational fluid dynamics models coupled to the motion of fish with prescribed deformation and examining the torque and power required along the fish body with two primary swimming modes. We find that the torque required by the hydrodynamic forces and body inertia exhibits a wave pattern that travels faster than the curvature wave in both anguilliform and carangiform swimmers, which can explain the traveling wave speeds of the muscle activations. Notably, intermittent negative power (i.e., power delivered by the fluid to the body) on the posterior part, along with a timely transfer of torque and energy by tendons, explains the decrease in the duration of muscle activation towards the tail. The torque contribution from the body elasticity further clarifies the wave speed increase or the reverse of the wave direction of the muscle activation on the posterior part of a carangiform swimmer. For anguilliform swimmers, the absence of the aforementioned changes in the muscle activation on the posterior part is consistent with our torque prediction and the absence of long tendons from experimental observations. These results provide novel insights into the functions of muscles and tendons as an integral part of the internal driving system, especially from an energy perspective, and they highlight the differences in the internal driving systems between the two primary swimming modes.

The "other" 15-40%: The Role of Non-Collagenous Extracellular Matrix Proteins and Minor Collagens in Tendon.

Extracellular matrix (ECM) determines the physiological function of all tissues, including musculoskeletal tissues. In tendon, ECM provides overall tissue architecture, which is tailored to match the biomechanical requirements of their physiological function, that is, force transmission from muscle to bone. Tendon ECM also constitutes the microenvironment that allows tendon-resident cells to maintain their phenotype and that transmits biomechanical forces from the macro-level to the micro-level. The structure and function of adult tendons is largely determined by the hierarchical organization of collagen type I fibrils. However, non-collagenous ECM proteins such as small leucine-rich proteoglycans (SLRPs), ADAMTS proteases, and cross-linking enzymes play critical roles in collagen fibrillogenesis and guide the hierarchical bundling of collagen fibrils into tendon fascicles. Other non-collagenous ECM proteins such as the less abundant collagens, fibrillins, or elastin, contribute to tendon formation or determine some of their biomechanical properties. The interfascicular matrix or endotenon and the outer layer of tendons, the epi- and paratenon, includes collagens and non-collagenous ECM proteins, but their function is less well understood. The ECM proteins in the epi- and paratenon may provide the appropriate microenvironment to maintain the identity of distinct tendon cell populations that are thought to play a role during repair processes after injury. The aim of this review is to provide an overview of the role of non-collagenous ECM proteins and less abundant collagens in tendon development and homeostasis. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:23-35, 2020.

Altered Strength Profile in Achilles Tendinopathy: A Systematic Review and Meta-Analysis.

Persistent strength deficits secondary to Achilles tendinopathy (AT) have been postulated to account for difficulty engaging in tendon-loading movements, such as running and jumping, and may contribute to the increased risk of recurrence. To date, little consensus exists on the presence of strength deficits in AT. Consequently, researchers are uncertain about the appropriate methods of assessment that may inform rehabilitation in clinical practice. To evaluate and synthesize the literature investigating plantar-flexion (PF) strength in individuals with AT. Two independent reviewers searched 9 electronic databases using an agreed-upon set of key words. Data were extracted from studies comparing strength measures (maximal, reactive, and explosive strength) between individuals with AT and healthy control participants or between the injured and uninjured sides of people with AT. The Critical Appraisal Skills Programme Case-Control Study Checklist was used to assess the risk of bias for the included studies. A total of 19 studies were eligible. Pooled meta-analyses for isokinetic dynamometry demonstrated reductions in maximal strength (concentric PF peak torque [PT] slow [Hedges g = 0.52, 44% deficit], concentric PF PT fast [Hedges g = 0.61, 38% deficit], and eccentric PF PT slow [Hedges g = 0.26, 18% deficit]). Reactive strength, particularly during hopping, was also reduced (Hedges g range = 0.32-2.61, 16%-35% deficit). For explosive strength, reductions in the rate of force development (Hedges g range = 0.31-1.73, 10%-21% deficit) were observed, whereas the findings for ground reaction force varied but were not consistently altered. Individuals with AT demonstrated strength deficits compared with the uninjured side or with asymptomatic control participants. Deficits were reported across the strength spectrum for maximal, reactive, and explosive strength. Clinicians and researchers may need to adapt their assessment of Achilles tendon function, which may ultimately help to optimize rehabilitation outcomes.

A Validated, Specimen-Specific Finite Element Model of the Supraspinatus Tendon Mechanical Environment.

Rotator cuff tears are a significant clinical problem previously investigated by unvalidated computational models that either use simplified geometry or isotropic elastic material properties to represent the tendon. The objective of this study was to develop an experimentally validated, finite element model of supraspinatus tendon using specimen-specific geometry and inhomogeneous material properties to predict strains in intact supraspinatus tendon at multiple abduction angles. Three-dimensional tendon surface strains were determined at 60 deg, 70 deg, and 90 deg of glenohumeral abduction for articular and bursal surfaces of supraspinatus tendon during cyclic loading (5-200 N, 50 cycles, 20 mm/min) to serve as validation data for computational model predictions. A finite element model was developed using the tendon geometry and inhomogeneous material properties to predict surface strains for loading conditions mimicking experimental loading conditions. Experimental strains were directly compared with computational model predictions to validate the model. Overall, the model successfully predicted magnitudes of strains that were within the experimental repeatability of 3% strain of experimental measures on both surfaces of the tendon. Model predictions and experiments showed the largest strains to be located on the articular surface (∼8% strain) between the middle and the anterior edge of the tendon. Importantly, the reference configuration chosen to calculate strains had a significant effect on strain calculations, and therefore, must be defined with an innovative optimization algorithm. This study establishes a rigorously validated specimen-specific (both geometry and material properties) computational model using novel surface strain measurements for the use in investigating the function of the supraspinatus tendon and to ultimately predict the propagation of supraspinatus tendon tears based on the tendon's mechanical environment.

Tendon tissue microdamage and the limits of intrinsic repair

The transmission of mechanical muscle force to bone for musculoskeletal stability and movement is one of the most important functions of tendon. The load-bearing tendon core is composed of highly aligned collagen-rich fascicles interspersed with stromal cells (tenocytes). Despite being built to bear very high mechanical stresses, supra-physiological/repetitive mechanical overloading leads to tendon microdamage in fascicles, and potentially to tendon disease and rupture. To date, it is unclear to what extent intrinsic healing mechanisms of the tendon core compartment can repair microdamage. In the present study, we investigated the healing capacity of the tendon core compartment in an ex vivo tissue explant model. To do so, we isolated rat tail tendon fascicles, damaged them by applying a single stretch to various degrees of sub-rupture damage and longitudinally assessed downstream functional and structural changes over a period of several days. Functional damage was assessed by changes in the elastic modulus of the material stress-strain curves, and biological viability of the resident tenocytes. Structural damage was quantified using a fluorescent collagen hybridizing peptide (CHP) to label mechanically disrupted collagen structures. While we observed functional mechanical damage for strains above 2% of the initial fascicle length, structural collagen damage was only detectable for 6% strain and beyond. Minimally loaded/damaged fascicles (2–4% strain) progressively lost elastic modulus over the course of tissue culture, despite their collagen structures remaining intact with high degree of maintained cell viability. In contrast, more severely overloaded fascicles (6–8% strain) with damage at the molecular/collagen level showed no further loss of the elastic modulus but markedly decreased cell viability. Surprisingly, in these heavily damaged fascicles the elastic modulus partially recovered, an effect also seen in further experiments on devitalized fascicles, implying the possibility of a non-cellular but matrix-driven mechanism of molecular repair. Overall, our findings indicate that the tendon core has very little capacity for self-repair of microdamage. We conclude that stromal tenocytes likely do not play a major role in anabolic repair of tendon matrix microdamage, but rather mediate catabolic matrix breakdown and communication with extrinsic cells that are able to effect tissue repair.

Effects of Type II Diabetes Mellitus on Tendon Homeostasis and Healing.

Over 300,000 tendon repairs are performed annually in the United States to repair damage to tendons as a result of either acute trauma or chronic tendinopathy. Individuals with type II diabetes mellitus (T2DM) are four times more likely to experience tendinopathy, and up to five times more likely to experience a tendon tear or rupture than non-diabetics. As nearly 10% of the US population is diabetic, with an additional 33% pre-diabetic, this is a particularly problematic health care challenge. Tendon healing in general is challenging and often unsatisfactory due to the formation of mechanically inferior scar-tissue rather than regeneration of native tendon structure. In T2DM tendons, there is evidence of an amplified scar tissue response, which may be associated with the increased the risk of rupture or impaired restoration of range of motion. Despite the dramatic effect of T2DM on tendon function and outcomes following injury, there are few therapies available to promote improved healing in these patients. Several recent studies have enhanced our understanding of the pro-inflammatory environment of T2DM healing and have assessed potential treatment approaches to mitigate pathological progression in pre-clinical models of diabetic tendinopathy. This review discusses the current state of knowledge of diabetic tendon healing from molecular to mechanical disruptions and identifies promising approaches and critical knowledge gaps as the field moves toward identification of novel therapeutic strategies to maintain or restore tendon function in diabetic patients. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:13-22, 2020.

Cell non-autonomous functions of S100a4 drive fibrotic tendon healing.

Identification of pro-regenerative approaches to improve tendon healing is critically important as the fibrotic healing response impairs physical function. In the present study we tested the hypothesis that S100a4 haploinsufficiency or inhibition of S100a4 signaling improves tendon function following acute injury and surgical repair in a murine model. We demonstrate that S100a4 drives fibrotic tendon healing primarily through a cell non-autonomous process, with S100a4 haploinsufficiency promoting regenerative tendon healing. Moreover, inhibition of S100a4 signaling via antagonism of its putative receptor, RAGE, also decreases scar formation. Mechanistically, S100a4 haploinsufficiency decreases myofibroblast and macrophage content at the site of injury, with both cell populations being key drivers of fibrotic progression. Moreover, S100a4-lineage cells become α-SMA+ myofibroblasts, via loss of S100a4 expression. Using a combination of genetic mouse models, small molecule inhibitors and in vitro studies we have defined S100a4 as a novel, promising therapeutic candidate to improve tendon function after acute injury.

Mechanical and Biochemical Stimulation of 3D Multilayered Scaffolds for Tendon Tissue Engineering.

Tendon injuries are frequent and occur in the elderly, young, and athletic populations. The inadequate number of donors combined with many challenges associated with autografts, allografts, xenografts, and prosthetic devices have added to the value of engineering biological substitutes, which can be implanted to repair the damaged tendons. Electrospun scaffolds have the potential to mimic the native tissue structure along with desired mechanical properties and, thus, have attracted noticeable attention. In order to improve the biological responses of these fibrous structures, we designed and fabricated 3D multilayered composite scaffolds, where an electrospun nanofibrous substrate was coated with a thin layer of cell-laden hydrogel. The whole construct composition was optimized to achieve adequate mechanical and physical properties as well as cell viability and proliferation. Mesenchymal stem cells (MSCs) were differentiated by the addition of bone morphogenetic protein 12 (BMP-12). To mimic the natural function of tendons, the cell-laden scaffolds were mechanically stimulated using a custom-built bioreactor. The synergistic effect of mechanical and biochemical stimulation was observed in terms of enhanced cell viability, proliferation, alignment, and tenogenic differentiation. The results suggested that the proposed constructs can be used for engineering functional tendons.

Mechanical properties, physiological behavior, and function of aponeurosis and tendon

During human movement, the muscle and tendinous structures interact as a mechanical system in which forces are generated and transmitted to the bone and energy is stored and released to optimize function and economy of movement and/or to reduce risk of injury. The present review addresses certain aspects of how the anatomical design and mechanical and material properties of the force-transmitting tissues contribute to the function of the muscle-tendon unit and thus overall human function. The force-bearing tissues are examined from a structural macroscopic point of view down to the nanoscale level of the collagen fibril. In recent years, the understanding of in vivo mechanical function of the force-bearing tissues has increased, and it has become clear that these tissues adapt to loading and unloading and furthermore that force transmission mechanics is more complex than previously thought. Future investigations of the force-transmitting tissues in three dimensions will enable a greater understanding of the complex functional interplay between muscle and tendon, with relevance for performance, injury mechanisms, and rehabilitation strategies.

Adaptation of Tendon Structure and Function in Tendinopathy With Exercise and Its Relationship to Clinical Outcome

Exercise is seen as the most evidence-based treatment for managing tendinopathy and although the type of exercise used to manage tendinopathy may induce adaptation in healthy tendons, it is not clear whether these adaptations occur in tendinopathy and if so whether they are associated with improved clinical outcomes. The aim of the study was to synthesize available evidence for adaptation of the Achilles tendon to eccentric exercise and the relationship between adaptation (change in tendon thickness) and clinical outcomes among people with Achilles tendinopathy. The search was performed in September 2018 in several databases. Studies investigating the response (clinical outcome and imaging on ultrasound/magnetic resonance imaging) of pathological tendons (tendinopathy, tendinosis, and partial rupture) to at least 12 weeks of eccentric exercise were included. Multiple studies that investigated the same interventions and outcome were pooled and presented in effect size estimates, mean difference, and 95% confidence intervals if measurement scales were the same, or standard mean difference and 95% confidence intervals if measurements scales were different. Where data could not be pooled the studies were qualitatively synthesized based on van Tulder etal. Eight studies met the inclusion and exclusion criteria and were included in the review. There was strong evidence that Achilles tendon thickness does not decrease in parallel with improved clinical outcomes. Whether a longer time to follow-up is more important than the intervention (ie,just the time per se) for a change in tendon thickness remains unknown. Future studies should investigate whether exercise (or other treatments) can be tailored to optimize tendon adaptation and function, and whether this relates to clinical outcomes.

Validity and reliability of measurements of aponeurosis dimensions from magnetic resonance images

Muscle performance is closely related to the structure and function of tendons and aponeuroses, the sheet-like, intramuscular parts of tendons. The architecture of aponeuroses has been difficult to study with magnetic resonance imaging (MRI) because these thin, collagen-rich connective tissues have very short transverse relaxation (T2) times and therefore provide a weak signal with conventional MRI sequences. Here, we validated measurements of aponeurosis dimensions from two MRI sequences commonly used in muscle-tendon research (mDixon and T1-weighted images), and an ultrashort echo time (UTE) sequence designed for imaging tissues with short T2 times. MRI-based measurements of aponeurosis width, length, and area of 20 sheep leg muscles were compared to direct measurements made with three-dimensional (3D) quantitative microdissection. The errors in measurement of aponeurosis width relative to the mean width were 1.8% for UTE, 3.7% for T1, and 18.8% for mDixon. For aponeurosis length, the errors were 7.6% for UTE, 1.9% for T1, and 21.0% for mDixon. Measurements from T1 and UTE scans were unbiased, but mDixon scans systematically underestimated widths, lengths, and areas of the aponeuroses. Using the same methods, we then found high inter-rater reliability (intraclass correlation coefficients >0.92 for all measures) of measurements of the dimensions of the central aponeurosis of the human tibialis anterior muscle from T1-weighted scans. We conclude that valid and reliable measurements of aponeurosis dimensions can be obtained from UTE and from T1-weighted scans. When the goal is to study the macroscopic architecture of aponeuroses, UTE does not hold an advantage over T1-weighted imaging.

Asymmetric Z-Tendon Shortening to Maximize Excision of Abnormal Tendon Tissue: A Technique Tip to Treat Elongated Tendons With Pathology

Operative treatment for a diseased or elongated Achilles tendon often involves resection of diseased tissue and Achilles tendon shortening. If the amount of diseased tissue is minimal, a traditional Z-shortening technique can be used to achieve appropriate tendon repair and function, which involves making an incision along the longitudinal axis mid-substance of the Achilles tendon. This technique is limited in its ability to resect abnormal tissue due to the placement of the incision traditionally along the midline of the tendon. In this chapter we describe an original modification of the Z-shortening technique to allow for the flexibility to resect pathologic tendon tissue and preserve more normal tissue. Level of Evidence: Diagnostic Level V. See Instructions for Authors for a complete description of levels of evidence.

Endoscopically Assisted Reconstruction of Posterior Tibial Tendon for Stage 2 Posterior Tibial Tendon Dysfunction

The posterior tibial tendon functions as a primary stabilizer of the medial longitudinal arch of the foot. Posterior tibial tendon dysfunction accounts for 80% of cases of adult-acquired flatfoot deformity. It is classified into 4 stages based on the function of the tibialis posterior tendon, the reducibility of the deformity, and the condition of the ankle joint. The purpose of this Technical Note is to describe the technical details of endoscopically assisted reconstruction of theposterior tibial tendon for stage 2 posterior tibial tendon dysfunction. It consists of using the medial half of the anterior tibialis tendon as a primary transfer and augmentation by the flexor digitorum longus. This construct is then protected with a subtalar arthroereisis.

Current trends in tendinopathy management.

Tendinopathy (pain and dysfunction in a tendon) is a prevalent clinical musculoskeletal presentation across the age spectrum, mostly in active and sporting people. Excess load above the tendon's usual capacity is the primary cause of clinical presentation. The propensity towards chronicity and the extended times for recovery and optimal function and the challenge of managing tendinopathy in a sporting competition season make this a difficult condition to treat. Tendinopathy is a heterogeneous condition in terms of its pathology and clinical presentation. Despite ongoing research, there is no consensus on tendon pathoetiology and the complex relationship between tendon pathology, pain and function is incompletely understood. The diagnosis of tendinopathy is primarily clinical, with imaging only useful in special circumstances. There has been a surge of tendinopathy treatments, most of which are poorly supported and warrant further exploration. The evidence supports a slowly progressive loading program, rather than complete rest, with other treatment modalities used as adjuncts mainly targeted at achieving pain relief.

Hydroxycamptothecin Prevents Fibrotic Pathways in Fibroblasts In Vitro.

Peritendinous fibrosis, which leads to impaired tendon function, is a clinical problem worldwide, and it is urgent to explore potential ways to reduce the formation of peritendinous adhesion. Several studies have demonstrated the biological roles of hydroxycamptothecin (HCPT) in inhibiting fibrosis in different tissues. In this study, we investigated whether HCPT could inhibit tendon fibrosis in vitro. Our results revealed that HCPT inhibited transforming growth factor (TGF)-β1-induced cell viability of human fibroblasts, decreased excessive cell hyperproliferation and promoted fibroblasts apoptosis. In addition, HCPT treatment also inhibited expression of fibrosis genes COL3A1 and α-smooth muscle actin (α-SMA). In terms of mechanism, we pretreated fibroblasts with the endoplasmic reticulum stress (ER) inhibitor salubrinal and RNA-dependent protein kinase-like ER kinase (PERK) short hairpin RNA, these treatments abolished the inhibitory effects of HCPT on fibrosis, thereby suggesting that HCPT's inhibition of TGF-β1-induced tendon fibrosis might be mediated by the PERK signaling pathway in vitro. In conclusion, our results suggested that HCPT had protective effects on peritendinous tissue fibrosis and might be promising in future clinical applications. © 2019 IUBMB Life, 71(5):653-662, 2019.

Isometric training and long-term adaptations: Effects of muscle length, intensity, and intent: A systematic review.

Isometric training is used in the rehabilitation and physical preparation of athletes, special populations, and the general public. However, little consensus exists regarding training guidelines for a variety of desired outcomes. Understanding the adaptive response to specific loading parameters would be of benefit to practitioners. The objective of this systematic review, therefore, was to detail the medium- to long-term adaptations of different types of isometric training on morphological, neurological, and performance variables. Exploration of the relevant subject matter was performed through MEDLINE, PubMed, SPORTDiscus, and CINAHL databases. English, full-text, peer-reviewed journal articles and unpublished doctoral dissertations investigating medium- to long-term (≥3weeks) adaptations to isometric training in humans were identified. These studies were evaluated further for methodological quality. Twenty-six research outputs were reviewed. Isometric training at longer muscle lengths (0.86%-1.69%/week, ES=0.03-0.09/week) produced greater muscular hypertrophy when compared to equal volumes of shorter muscle length training (0.08%-0.83%/week, ES=-0.003 to 0.07/week). Ballistic intent resulted in greater neuromuscular activation (1.04%-10.5%/week, ES=0.02-0.31/week vs 1.64%-5.53%/week, ES=0.03-0.20/week) and rapid force production (1.2%-13.4%/week, ES=0.05-0.61/week vs 1.01%-8.13%/week, ES=0.06-0.22/week). Substantial improvements in muscular hypertrophy and maximal force production were reported regardless of training intensity. High-intensity (≥70%) contractions are required for improving tendon structure and function. Additionally, long muscle length training results in greater transference to dynamic performance. Despite relatively few studies meeting the inclusion criteria, this review provides practitioners with insight into which isometric training variables (eg, joint angle, intensity, intent) to manipulate to achieve desired morphological and neuromuscular adaptations.