Biochemical and morphological modifications in rabbit Achilles tendon during maturation and ageing.
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ABSTRACT:
SUBMITTER: Cetta G
PROVIDER: S-EPMC1158315 | biostudies-other | 1982 Apr
REPOSITORIES: biostudies-other
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Project description:INTRODUCTION:The risk of tendon injury and disease increases significantly with increasing age. The aim of the study was to characterise transcriptional changes in human Achilles tendon during the ageing process in order to identify molecular signatures that might contribute to age-related degeneration. METHODS:RNA for gene expression analysis using RNA-Seq and quantitative real-time polymerase chain reaction analysis was isolated from young and old macroscopically normal human Achilles tendon. RNA sequence libraries were prepared following ribosomal RNA depletion, and sequencing was undertaken by using the Illumina HiSeq 2000 platform. Expression levels among genes were compared by using fragments per kilobase of exon per million fragments mapped. Differentially expressed genes were defined by using Benjamini-Hochberg false discovery rate approach (P<0.05, expression ratios 1.4 log2 fold change). Alternative splicing of exon variants were also examined by using Cufflinks. The functional significance of genes that showed differential expression between young and old tendon was determined by using ingenuity pathway analysis. RESULTS:In total, the expression of 325 transcribed elements, including protein-coding transcripts and non-coding transcripts (small non-coding RNAs, pseudogenes, long non-coding RNAs and a single microRNA), was significantly different in old compared with young tendon (±1.4 log2 fold change, P<0.05). Of these, 191 were at higher levels in older tendon and 134 were at lower levels in older tendon. The top networks for genes differentially expressed with tendon age were from cellular function, cellular growth, and cellular cycling pathways. Notable differential transcriptome changes were also observed in alternative splicing patterns. Several of the top gene ontology terms identified in downregulated isoforms in old tendon related to collagen and post-translational modification of collagen. CONCLUSIONS:This study demonstrates dynamic alterations in RNA with age at numerous genomic levels, indicating changes in the regulation of transcriptional networks. The results suggest that ageing is not primarily associated with loss of ability to synthesise matrix proteins and matrix-degrading enzymes. In addition, we have identified non-coding RNA genes and differentially expressed transcript isoforms of known matrix components with ageing which require further investigation.
| S-EPMC4355574 | biostudies-literature
Project description:The Achilles tendon exhibits anatomical variations in subtendon twist among individuals, and its compliance can change due to conditions like Achilles tendinopathy. However, current musculoskeletal models overlook these material and morphological variations. This study aimed to investigate the impact of altering Achilles subtendon insertion points and compliance on the triceps surae muscle forces, and therefore tendon loading, during dynamic exercises in one Achilles tendinopathy patient. First, subtendon insertion points were altered in the musculoskeletal model based on a subject-specific 3D freehand ultrasound model and for three types of subtendon twists: low, medium, and high. Second, tendon compliance was modeled based on experimental values, creating three musculoskeletal models: compliant, mean, and stiff. Results indicated that tendon compliance had a larger effect than tendon twist on triceps surae muscle forces. Altering subtendon insertion points to the three types of twist showed a maximal change of 2.3% in muscle force contribution compared to the no-twist model. During the eccentric rehabilitation exercise-a common exercise choice during rehabilitation-the compliant tendon model showed substantial differences compared to the generic (control) musculoskeletal model, resulting in decreased gastrocnemius medialis (-3.5%) and gastrocnemius lateralis (-3.2%) contributions and increased soleus contribution (+ 6.6%). Our study results highlight the necessity of incorporating tendon compliance in musculoskeletal models to accurately predict triceps surae muscle forces, especially in individuals with increased tendon compliance, such as patients with Achilles tendinopathy. Such findings contribute to more accurate predictions of muscle forces and hence, personalized rehabilitation strategies.
| S-EPMC11291231 | biostudies-literature
Project description:Tendons are hypocellular and hypovascular tissues, and thus, their natural healing capacity is low. In this study, we sought to evaluate the efficacy of platelet-rich fibrin (PRF) to serve as a bioactive scaffold in promoting the healing of rabbit Achilles tendon injury. For in vitro study, the essence portion of PRF was determined through bioluminescent assay. Furthermore, we analyzed the time-sequential cytokines-release kinetics of PRF and evaluated their effects on tenocytes proliferation and tenogenic gene expressions. In animal study, the rabbit Achilles tendon defect was left untreated or implanted with normal/heat-denatured PRF scaffolds. Six weeks postoperatively, the specimens were evaluated through sonographic imaging and histological analysis. The results revealed significantly more activated platelets on bottom half of the PRF scaffold. Cytokine concentrations released from PRF could be detected from the first hour to six days. For the in vitro study, PRF enhanced cell viability and collagen I, collagen III, tenomodulin, and tenascin gene expression compared to the standard culture medium. For in vivo study, sonographic images revealed significantly better tendon healing in the PRF group in terms of tissue echogenicity and homogeneity. The histological analysis showed that the healing tissues in the PRF group had more organized collagen fiber, less vascularity, and minimal cartilage formation. In conclusion, bioactive PRF promotes in vitro tenocytes viability and tenogenic phenotypic differentiation. Administration of a PRF scaffold at the tendon defect promotes tissue healing as evidenced by imaging and histological outcomes.
| S-EPMC7247336 | biostudies-literature
Project description:BackgroundDuring the stance phase of running, the elasticity of the Achilles tendon enables the utilisation of elastic energy and allows beneficial contractile conditions for the triceps surae muscles. However, the effect of changes in tendon mechanical properties induced by chronic loading is still poorly understood. We tested the hypothesis that a training-induced increase in Achilles tendon stiffness would result in reduced tendon strain during the stance phase of running, which would reduce fascicle strains in the triceps surae muscles, particularly in the mono-articular soleus.MethodsEleven subjects were assigned to a training group performing isometric single-leg plantarflexion contractions three times per week for ten weeks, and another ten subjects formed a control group. Before and after the training period, Achilles tendon stiffness was estimated, and muscle-tendon mechanics were assessed during running at preferred speed using ultrasonography, kinematics and kinetics.ResultsAchilles tendon stiffness increased by 18% (P < 0.01) in the training group, but the associated reduction in strain seen during isometric contractions was not statistically significant. Tendon elongation during the stance phase of running was similar after training, but tendon recoil was reduced by 30% (P < 0.01), while estimated tendon force remained unchanged. Neither gastrocnemius medialis nor soleus fascicle shortening during stance was affected by training.DiscussionThese results show that a training-induced increase in Achilles tendon stiffness altered tendon behaviour during running. Despite training-induced changes in tendon mechanical properties and recoil behaviour, the data suggest that fascicle shortening patterns were preserved for the running speed that we examined. The asymmetrical changes in tendon strain patterns supports the notion that simple in-series models do not fully explain the mechanical output of the muscle-tendon unit during a complex task like running.
| S-EPMC6486809 | biostudies-literature
Project description:One great challenge in surgical tendon repair is the minimization of peritendinous adhesions. An electrospun tube can serve as a physical barrier around a conventionally sutured tendon. Six New Zealand White rabbits had one Achilles tendon fully transsected and sutured by a 4-strand suture. Another six rabbits had the same treatment, but with the additional electrospun DegraPol tube set around the sutured tendon. The adhesion formation to the surrounding tissue was investigated 12 weeks post-operation. Moreover, inflammation-related protease-activated receptor-2 (PAR-2) protein expression was assessed. Finally, rabbit Achilles tenocyte cultures were exposed to platelet-derived growth factor-BB (PDGF-BB), which mimicks the tendon healing environment, where PAR-2 gene expression was assessed as well as immunofluorescent staining intensity for F-actin and α-tubulin, respectively. At 12 weeks post-operation, the partially degraded DegraPol tube exhibited significantly lower adhesion formation (- 20%). PAR-2 protein expression was similar for time points 3 and 6 weeks, but increased at 12 weeks post-operation. In vitro cell culture experiments showed a significantly higher PAR-2 gene expression on day 3 after exposure to PDGF-BB, but not on day 7. The cytoskeleton of the tenocytes changed upon PDGF-BB stimulation, with signs of reorganization, and significantly decreased F-actin intensity. An electrospun DegraPol tube significantly reduces adhesion up to twelve weeks post-operation. At this time point, the tube is partially degraded, and a slight PAR-2 increase was detected in the DP treated tendons, which might however arise from particles of degrading DegraPol that were stained dark brown. PAR-2 gene expression in rabbit tenocytes reveals sensitivity at around day 10 after injury.
| S-EPMC8639666 | biostudies-literature
Project description:Acute and chronic tendinopathies remain clinically challenging and tendons are predisposed to degeneration or injury with age. Despite the high prevalence of tendon disease in the elderly, our current understanding of the mechanisms underlying the age-dependent deterioration of tendon function remains very limited. Here, we show that Secreted protein acidic and rich in cysteine (Sparc) expression significantly decreases in healthy-aged mouse Achilles tendons. Loss of Sparc results in tendon collagen fibrillogenesis defects and Sparc-/- tendons are less able to withstand force in comparison with their respective wild type counterparts. On the cellular level, Sparc-null and healthy-aged tendon-derived cells exhibited a more contracted phenotype and an altered actin cytoskeleton. Additionally, an elevated expression of the adipogenic marker genes PPARγ and Cebpα with a concomitant increase in lipid deposits in aged and Sparc-/- tendons was observed. In summary, we propose that Sparc levels in tendons are critical for proper collagen fibril maturation and its age-related decrease, together with a change in ECM properties favors lipid accretion in tendons.
| S-EPMC5009305 | biostudies-literature
Project description:In the treatment of acute Achilles tendon rupture, recent studies demonstrate that conservative treatment with functional rehabilitation provides good results, with nearly identical postoperative rerupture rates when compared with surgical treatment. Surgical treatment is indicated in patients with particular conditions, such as patients who are young active athletes who require early return to play or those who wish to avoid the muscle atrophy associated with conservative methods. If surgery is the selected option for treatment, the postoperative complications of each type of surgery must be considered. In conventional open repair, the most common complication is soft-tissue infection due to the high tension of soft tissue affected from the bowstring of the repaired tendon being kept in the equinus position of the ankle. For percutaneous methods, sural nerve entrapment and injury are the most commonly reported complications. Other methods, including endoscopy, require technical expertise as well as special equipment. Several types of combination approaches have been explored in the literature. We describe a combined open and percutaneous technique to repair the Achilles tendon, called the hybrid Achilles tendon repair. This technique has been developed to provide a simplified and reproducible method of hybrid repair in which the complications of previous methods are avoided and which can be done without special equipment.
| S-EPMC6019910 | biostudies-literature
Project description:The evaluation of in vivo muscle-tendon loads is fundamental to understanding the actuation of normal and pathological human walking. However, conventional techniques for measuring muscle-tendon loads in the human body are too invasive for use in gait analysis. Here, we demonstrate the use of noninvasive measures of shear wave propagation as a proxy for Achilles tendon loading during walking. Twelve healthy young adults performed isometric ankle plantarflexion on a dynamometer. Achilles tendon wave speed, tendon moment arms, tendon cross-sectional area and ankle torque were measured. We first showed that the linear relationship between tendon stress and wave speed squared can be calibrated from isometric tasks. There was no significant effect of knee angle, ankle angle or loading rate on the subject-specific calibrations. Calibrated shear wave tensiometers were used to estimate Achilles tendon loading when walking at speeds ranging from 1 to 2 m/s. Peak tendon stresses during pushoff increased from 41 to 48 MPa as walking speed was increased, and were comparable to estimates from inverse dynamics. The tensiometers also detected Achilles tendon loading of 4 to 7 MPa in late swing. Late swing tendon loading was not discernible in the inverse dynamics estimates, but did coincide with passive stretch of the gastrocnemius muscle-tendon units. This study demonstrates the capacity to use calibrated shear wave tensiometers to evaluate tendon loading in locomotor tasks. Such technology could prove beneficial for identifying the muscle actions that underlie subject-specific movement patterns.
| S-EPMC6748912 | biostudies-literature
Project description:PurposeTo evaluate differences of Achilles tendon (AT) hardness and morphology between asymptomatic tendons in patients with acute AT ruptures on the contralateral side and asymptomatic tendons in healthy people by using computer-assisted quantification on axial-strain sonoelastography (ASE).MethodsThe study consisted of 33 asymptomatic tendons in 33 patients (study group) and 34 tendons in 19 healthy volunteers (control group). All the tendons were examined by both ASE and conventional ultrasound. Computer-assisted quantification on ASE was applied to extract hardness variables, including the mean (Hmean), 20th percentile (H20), median (H50) and skewness (Hsk) of the hardness within tendon, and the ratio of the mean hardness within tendon to that outside tendon (Hratio) and three morphological variables: the thickness (THK), cross-sectional area, and eccentricity (ECC) of tendons.ResultsThe Hmean, Hsk, H20, H50, and Hratio in the proximal third of the tendon body in study group were significantly smaller than those in control group (Hmean: 0.43±0.09 vs 0.50±0.07, p=0.001; Hsk: -0.53±0.51 vs -1.09±0.51, p<0.001; H20: 0.31±0.10 vs 0.40±0.10, p=0.001; H50: 0.45±0.10 vs 0.53±0.08, p<0.001; Hratio: 1.01±0.25 vs 1.20±0.23, p=0.003). The THK and cross-sectional area of tendons in the study group were larger than those in the control group (p<0.05).ConclusionsAs a quantitative objective method, the computer-assisted ASE reveals that the asymptomatic ATs contralateral to acute rupture are softer than those of healthy control group at the proximal third and the asymptomatic tendons in people with rupture history are thicker, larger, and rounder than those of normal volunteers especially at the middle and distal thirds of AT body.
| S-EPMC6304598 | biostudies-literature
Project description:During rapid deceleration of the body, tendons buffer part of the elongation of the muscle-tendon unit (MTU), enabling safe energy dissipation via eccentric muscle contraction. Yet, the influence of changes in tendon stiffness within the physiological range upon these lengthening contractions is unknown. This study aimed to examine the effect of training-induced stiffening of the Achilles tendon on triceps surae muscle-tendon behavior during a landing task. Twenty-one male subjects were assigned to either a 10-week resistance-training program consisting of single-leg isometric plantarflexion (n = 11) or to a non-training control group (n = 10). Before and after the training period, plantarflexion force, peak Achilles tendon strain and stiffness were measured during isometric contractions, using a combination of dynamometry, ultrasound and kinematics data. Additionally, testing included a step-landing task, during which joint mechanics and lengths of gastrocnemius and soleus fascicles, Achilles tendon, and MTU were determined using synchronized ultrasound, kinematics and kinetics data collection. After training, plantarflexion strength and Achilles tendon stiffness increased (15 and 18%, respectively), and tendon strain during landing remained similar. Likewise, lengthening and negative work produced by the gastrocnemius MTU did not change detectably. However, in the training group, gastrocnemius fascicle length was offset (8%) to a longer length at touch down and, surprisingly, fascicle lengthening and velocity were reduced by 27 and 21%, respectively. These changes were not observed for soleus fascicles when accounting for variation in task execution between tests. These results indicate that a training-induced increase in tendon stiffness does not noticeably affect the buffering action of the tendon when the MTU is rapidly stretched. Reductions in gastrocnemius fascicle lengthening and lengthening velocity during landing occurred independently from tendon strain. Future studies are required to provide insight into the mechanisms underpinning these observations and their influence on energy dissipation.
| S-EPMC6028711 | biostudies-literature