Development Of Tendinopathy Research Articles

A high glucose level stimulate inflammation and weaken pro-resolving response in tendon cells – A possible factor contributing to tendinopathy in diabetic patients

BackgroundTendinopathy is a chronic disorder that affects a huge population, and is causing high socioeconomical impacts worldwide. Tendinopathy was reported to be more prevalent in diabetic patients, and chronic inflammation was proposed to play an important role in its development. It was also known that diabetic patients present in a pro-inflammatory state. There is a possibility that the high glucose environment in diabetic patients lead to chronic inflammation in the tendon, and eventually the development of tendinopathy. In this study, we would simulate the diabetic environment in an in vitro setup, to assess the effect of a high glucose level on cultured tendinopathic and healthy tendon derived stem cells (TDSCs) under inflammatory stress. We would first like to assess whether there are differences between the inflammatory response in tendinopathic and healthy TDSCs. We would then investigate whether a high glucose level may lead to changes in the inflammatory response in healthy tendon cells. MethodsTendinopathic TDSCs were cultured from 2 torn rotator cuff tendons and 1 ruptured patellar tendon. Healthy TDSCs were cultured from 3 gender matched healthy hamstring tendons. Cells were stimulated by either 2ng/ml IL-1B for 24 hours, 11.1 mmol/L glucose for 24 hours, or both. mRNA was collected and processed for qPCR targeting B-actin, ALOX12, ALOX15, FPR1, FPR2, ChemR23, and COX2. ResultsUpregulation of FPR1 (p=0.050) ChemR23 (p=0.050), ALOX15 (p=0.050) was significantly weakened when comparing tendinopathic and healthy TDSCs stimulated with IL-1b. The upregulation of ALOX15 (p=0.050), was significantly lower in stimulated healthy TDSCs in a high glucose environment when comparing with those stimulated under a regular glucose level. A high glucose level also induced upregulation of COX2 (p=0.046) in healthy TDSCs and tendinopathic TDSCs (p=0.050). ConclusionThe results of this study provide a possible explanation to the increased risk to develop tendinopathy in diabetic patients. Chronic inflammation observed in tendinopathy may be due to the weakening of pro-resolving responses in tendinopathic TDSCs, and a high glucose environment may lead to chronic inflammation and ultimately tendinopathy by persistent stimulation and weakening of pro-resolving response in healthy TDSCs.

HMGB1 mediates the development of tendinopathy due to mechanical overloading

Mechanical overloading is a major cause of tendinopathy, but the underlying pathogenesis of tendinopathy is unclear. Here we report that high mobility group box1 (HMGB1) is released to the tendon extracellular matrix and initiates an inflammatory cascade in response to mechanical overloading in a mouse model. Moreover, administration of glycyrrhizin (GL), a naturally occurring triterpene and a specific inhibitor of HMGB1, inhibits the tendon’s inflammatory reactions. Also, while prolonged mechanical overloading in the form of long-term intensive treadmill running induces Achilles tendinopathy in mice, administration of GL completely blocks the tendinopathy development. Additionally, mechanical overloading of tendon cells in vitro induces HMGB1 release to the extracellular milieu, thereby eliciting inflammatory and catabolic responses as marked by increased production of prostaglandin E2 (PGE2) and matrix metalloproteinase-3 (MMP-3) in tendon cells. Application of GL abolishes the cellular inflammatory/catabolic responses. Collectively, these findings point to HMGB1 as a key molecule that is responsible for the induction of tendinopathy due to mechanical overloading placed on the tendon.

Advanced Glycation End-Products Suppress Mitochondrial Function and Proliferative Capacity of Achilles Tendon-Derived Fibroblasts

Debilitating cases of tendon pain and degeneration affect the majority of diabetic individuals. The high rate of tendon degeneration persists even when glucose levels are well controlled, suggesting that other mechanisms may drive tendon degeneration in diabetic patients. The purpose of this study was to investigate the impact of advanced glycation end-products on tendon fibroblasts to further our mechanistic understanding of the development and progression of diabetic tendinopathy. We proposed that advanced glycation end-products would induce limitations to mitochondrial function and proliferative capacity in tendon-derived fibroblasts, restricting their ability to maintain biosynthesis of tendon extracellular matrix. Using an in-vitro cell culture system, rat Achilles tendon fibroblasts were treated with glycolaldehyde-derived advanced glycation end-products (0, 50, 100, and 200 μg/ml) for 48 hours in normal glucose (5.5 mM) and high glucose (25 mM) conditions. We demonstrate that tendon fibroblasts treated with advanced glycation end-products display reduced ATP production, electron transport efficiency, and proliferative capacity. These impairments were coupled with alterations in mitochondrial DNA content and expression of genes associated with extracellular matrix remodeling, mitochondrial energy metabolism, and apoptosis. Our findings suggest that advanced glycation end-products disrupt tendon fibroblast homeostasis and may be involved in the development and progression of diabetic tendinopathy.

Identification of Inflammatory Mediators in Tendinopathy Using a Murine Subacromial Impingement Model.

Subacromial impingement is associated with a spectrum of disorders-including rotator cuff disease-but their relationship is complex. We have established a novel murine model of subacromial impingement to study supraspinatus tendinopathy. The purpose of this study was to evaluate changes in gene expression in this murine shoulder impingement model to further elucidate the mechanisms underlying the development of tendinopathy. Twenty-eight C57BL/6 mice were used in this study. All mice underwent bilateral surgery with insertion of a small metal clip in the subacromial space or a sham procedure. The supraspinatus tendons underwent histological analyses, biomechanical testing, and RNA extraction for multiplex gene expression analysis (NanoString, Seattle, WA). Histology demonstrated increased cellularity and disorganized collagen fibers of the supraspinatus tendon in the clip impingement group. Mean load to failure (5.20 vs. 1.50 N, p < 0.001) and mean stiffness (4.95 vs. 1.47 N/mm, p < 0.001) were lower in the impingement group than the sham group. NanoString analyses revealed 111 differentially expressed genes (DEGs) between the impingement and sham groups. DEGs of interest included Mmp3 (expression ratio [ER]: 2.68, p = 0.002), Tgfb1 (ER: 1.76, p = 0.01), Col3a1 (ER: 1.66, p = 0.03), and Tgfbr2 (ER: 1.53, p = 0.01). Statement of clinical significance: We identified 111 DEGs that may contribute to the development of tendinopathy in this model. Further studies of these specific genes will allow identification of their roles in the initiation and regulation of tendon damage, and their potential to serve as novel therapeutic targets in the treatment of rotator cuff disease. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2575-2582, 2019.

Pressure changes in the Kager fat pad at the extremes of ankle motion suggest a potential role in Achilles tendinopathy.

The Kager fat pad is one of the largest soft tissue structures local to the ankle joint, yet it is poorly understood. It has been hypothesised to have a role in Achilles tendinopathy. This study aimed to investigate the pressure areas in the Kager fat pad adjacent to the Achilles tendon and to assess the anatomy and deformation of the Kager fat pad in cadavers. Twelve fresh frozen cadaveric ankles (mean age 44years, range 38-51) were mounted in a customized testing rig, enabling plantar flexion and dorsiflexion of the ankle, with the Achilles tendon loaded. A needle tipped pressure sensor was inserted in two areas of the Kager fat pad under ultrasound guidance (retrocalcaneal bursa and at 3cm proximal from Achilles insertion). Pressure readings were recorded at different flexion angles. Following testing, the specimens were dissected to expose the Kager fat pad and retrieve it for analysis. MRI images were also taken from three healthy volunteers and the Kager fat pad deformation examined. Mean pressures significantly increased in all specimens at terminal ankle plantar and dorsi flexion in both regions (p < 0.05). The Kager fat pad was consistently adherent to the Achilles at its posterior aspect for a mean length of 7.7cm (SD 0.27, 89% of KFP length). The most distal part of the Kager fat pad was the exception and it detached from the Achilles to give way to the retroalcaneal bursa for a mean length of 0.92cm (SD 0.24, 11% of KFP length). The bursal space is partially occupied by a constant 'wedge' extension of Kager fat pad. The mean volume of the whole Kager fat pad was 10.6ml (SD 3.37). Video and MRI demonstrated that the Kager fat pad undergoes significant deformation during plantar flexion as it is displaced superiorly by the Achilles, with the wedge being forced into the retrocalcaneal bursal space. The Kager fat pad does not remain static during ankle range of motion, but deforms and its pressure also changes. This observation supports the theory that it acts as a shock-absorber to the Achilles tendon and pathological changes to the fat pad may be clinically important in the development of Achilles tendinopathy.

Progress on relationship between transforming growth factor-beta1 and tendinopathy

As a common soft tissue disease, the mechanism of tendinopathy has not been clarified and is lack of effective treatment method. Change of tissue fibrosis is the one of the main pathological features. Transforming growth factor beta 1 (TGF-β1), which is one of the important factor, participated in fibrosis. Inconsonant expressions of TGF-β1 could be found in tendinopathy. The studies are still controversial, but the vast majority of studies had showed that TGF-β1 was abnormal, and it is given priority to increase, which means that TGF-β1 plays an important role in the process of tendinopathy. In the process of tendon injuries and repairs, the time of TGF-β1 increasing is inconsistent. The time for TGF-β1 plays a significant role has not been determined. TGF-β1 has abnormal expressions in both tendinopathy and tendon repairs, which are two opposite processes. Thus, it may not be a one-way adjustment factor, but has a pleiotropic. Recent studies showed that TGF-β1 was considered as binding to receptor and transferring signal into the cell. Now there are three different receptors are found. The classical pathway of TGF-β1 in intracellular signal transduction is mainly through activation of Smad pathway. In the same time, there are also some non-classical pathways. TGF-β1 could break balance of extracellular matrix, which may be a reason to cause tendinopathy. But the regulations of TGF-β1 on the extracellular matrix are complex and diverse, further studies are required. Existing researches showed that the performance of treatments on tendinopathy is unsatisfied by blocking TGF-β1 downstream pathway. Therefore, it is a good way to study the upstream mechanism of produce TGF-β1. It may be an effective method to find new targets to inhibit the development of tendinopathy better by finding the original source of TGF-β1.

Exogenous micro-RNA and antagomir modulate osteogenic gene expression in tenocytes

Tendinopathy is a common and disabling condition that is difficult to treat. The pathomolecular events behind tendinopathy remain uncertain. Micro-RNAs (miRNAs, miRs) are short non-coding RNAs that regulate gene expression and may play a role in tendinopathy development. Tenocytes were obtained from human patellar tendons in patients undergoing anterior cruciate ligament (ACL) reconstruction. Micro-RNA mimics and antagomirs for miR-30d, 26a, and 29a were separately transfected into tenocyte culture. Gene expression for scleraxis, collagen 1 alpha 1 (COL1A1), collagen 3 alpha 1 (COL3A1), interleukin-1-beta (IL-1β), interleukin-6 (IL-6), bone morphogenic protein 2 (BMP2), bone morphogenic protein 12 (BMP12), and osteocalcin was determined for each miRNA mimic and antagomir transfection using real-time quantitative PCR (qPCR). The results showed that exogenous miR-29a downregulated BMP2 and BMP12, while miR-26a and miR-30d did not have a significant effect on tenocyte gene expression. These findings suggest miR-29a contributes to tendon homeostasis and can serve as a potential therapeutic target in treating tendinopathy.

SUPRASPINATUS TENDON PATHOMECHANICS: A CURRENT CONCEPTS REVIEW

Tendinopathy of the supraspinatus muscle is a frequent cause of shoulder pain. Although it is a common condition, the pathophysiology is not fully understood. The purpose of this clinical commentary is to provide an overview of the pathophysiology of supraspinatus tendinopathy and discuss the conservative treatment solutions. Supraspinatus tendinopathy is thought to be caused by both intrinsic, and extrinsic factors. Structural and biological changes happen when tendinopathy develops. Cellular and extracellular modifications characterize tendon healing stages that continue over time. Assessment is paramount in order to differentiate the structure involved, and to offer a proper treatment solution. Knowledge of the general concepts regarding the development of supraspinatus tendinopathy, and of the healing process should guide physiotherapists when proposing treatment options. Physical modalities commonly utilized for supraspinatus tendinopathy such as: laser, ultrasound, and shock-wave therapy have little and contradictory evidence. Exercise in form of eccentric training may be considered as it seems to have beneficial effects, however, more research is needed.

Prediction of running-induced Achilles tendinopathy with pain sensitivity - a 1-year prospective study.

Background and aims Achilles tendinopathy is common among runners, but the etiology remains unclear. High mechanical pain sensitivity may be a predictor of increased risk of developing Achilles tendinopathy in this group. The purpose of this study was to investigate whether local pain sensitivity could predict the development of Achilles tendinopathy in recreational male runners. The overall hypothesis was that high pain sensitivity would be related to a higher risk of developing Achilles tendinopathy among recreational male runners. Methods Ninety-nine recreational male runners were recruited and followed prospectively for 1 year. At baseline and after 500 km of running the pressure pain threshold (PPT) was assessed at the infraspinatus and at the Achilles tendon (AT-PPT). Based on the AT-PPT at baseline, a median split was used to divide the runners into two groups. The high pain sensitivity groups was defined as runners displaying a pain pressure threshold below 441 kPa on the Achilles tendon, while the low pain sensitivity group was defined as runners displaying a pain pressure threshold above 441 kPa on the Achilles tendon, respectively. Subsequently, the cumulative risk difference between the two groups was assessed by using the pseudo-observation method. Results High pain sensitivity runners sustained 5%-point (95% CI: -0.18 to 0.08) more Achilles tendinopathy episodes during the first 1,500 km. No significant group differences in risk were found at 100, 250, 500, 1,000 and 1,500 km of running. Conclusions No significant association was found between mechanical pain sensitivity in the Achilles tendon and the risk of developing Achilles tendinopathy. However, the risk difference indicated a association between a high mechanical pain sensitivity and an increased risk of developing Achilles tendinopathy. It is plausible that changes in pain sensitivity were masked by unmeasured covariates, such as the differences in progression/regression of training volume and running speed between the two groups. This study was limited in size, which limited the possibility to account for covariates, such as differences in progression/regression of running speed between runners. With the limitations in mind, future studies should control the training volume, speed and running shoes in the design or account for it in the analysis. Implications Pain sensitivity of the Achilles tendon seems not to be related to an increased risk of developing Achilles pain in relation to running.

Tendon-Derived Stem Cell Differentiation in the Degenerative Tendon Microenvironment.

Tendinopathy is prevalent in athletic and many occupational populations; nevertheless, the pathogenesis of tendinopathy remains unclear. Tendon-derived stem cells (TDSCs) were regarded as the key culprit for the development of tendinopathy. However, it is uncertain how TDSCs differentiate into adipocytes, chondrocytes, or osteocytes in the degenerative microenvironment of tendinopathy. So in this study, the regulating effects of the degenerative tendon microenvironment on differentiation of TDSCs were investigated. TDSCs were isolated from rat Achilles tendons and were grown on normal and degenerative (prepared by stress-deprived culture) decellularized tendon slices (DTSs). Immunofluorescence staining, H&E staining, real-time PCR, and Western blot were used to delineate the morphology, proliferation, and differentiation of TDSCs in the degenerative microenvironment. It was found that TDSCs were much more spread on the degenerative DTSs than those on normal DTSs. The tenocyte-related markers, COL1 and TNMD, were highly expressed on normal DTSs than the degenerative DTSs. The expression of chondrogenic and osteogenic markers, COL2, SOX9, Runx2, and ALP, was higher on the degenerative DTSs compared with TDSCs on normal DTSs. Furthermore, phosphorylated FAK and ERK1/2 were reduced on degenerative DTSs. In conclusion, this study found that the degenerative tendon microenvironment induced TDSCs to differentiate into chondrogenic and osteogenic lineages. It could be attributed to the cell morphology changes and reduced FAK and ERK1/2 activation in the degenerative microenvironment of tendinopathy.

Impact de la santé buccodentaire sur les performances sportives

Overall good health is essential to improve training and performance, especially for elite athletes. However, a high prevalence of oral diseases as dental caries, dental erosion or gingivitis has been observed in the professional sport community. Moreover, according to several studies, poor oral health leads to difficulties in eating and sleeping and has a negative impact on quality of life and self-confidence. Periodontal diseases such as periodontitis seem to induce systemic inflammation. Therefore, oral diseases in the sport community may also affect athletic performance or even have an impact on the systemic level and potentially influence the development of tendinopathies. This literature review aims to identify the incidence of oral diseases in elite athlete and highlight the impact of oral health on athletic performances. Furthermore, oral health preventive measures and risk mitigation interventions will be proposed.

Characterization of a Novel Calcific Achilles Tendinopathy Model in Mice: Contralateral Tendinopathy Induced by Unilateral Tenotomy.

Achilles tendinopathy is a significant clinical disease characterized by activity-related pain, focal movement limitation, and intratendinous imaging changes. However, treatment of Achilles tendinopathy has been based mainly on theoretical rationale and clinical experience because of its unclear underlying pathogenesis and mechanism. The purpose of the study was to develop a simple but reproducible overuse-induced animal model of Achilles tendinopathy in mice to better understand the underlying mechanism and prevent calcific Achilles tendinopathy. A total of 80 C57/B6 mice (8 or 9weeks old) were employed and randomly divided into control and experimental groups. Unilateral Achilles tenotomy was performed on the right hind limbs in the experiment group. 12 weeks after unilateral Achilles tenotomy, the onset of Achilles tendinopathy in the contralateral Achilles tendon was determined by radiological assessment, histologic analysis, electron microscopy observation, and biomechanical test. The onset of calcific Achilles tendinopathy in contralateral Achilles tendon was confirmed after 12 weeks of unilateral tenotomy. The contralateral Achilles tendon in the experimental group was characterized as hypercellularity, neovascularization, and fused collagen fiber disarrangement, compared with the control group. Importantly, intra-tendon endochondral ossification and calcaneus deformity were featured in contralateral Achilles tendon. In addition, poor biomechanical properties in the contralateral Achilles tendon revealed the incidence of Achilles tendinopathy. We hereby introduce a novel, simple, but reproducible spontaneous contralateral calcific Achilles tendinopathy model in mice, which represents overuse conditions during tendinopathy development in humans. It should be a useful tool to further study the underlying pathogenesis of calcific Achilles tendinopathy.

Novel roles for scleraxis in regulating adult tenocyte function

BackgroundTendinopathies are common and difficult to resolve due to the formation of scar tissue that reduces the mechanical integrity of the tissue, leading to frequent reinjury. Tenocytes respond to both excessive loading and unloading by producing pro-inflammatory mediators, suggesting that these cells are actively involved in the development of tendon degeneration. The transcription factor scleraxis (Scx) is required for the development of force-transmitting tendon during development and for mechanically stimulated tenogenesis of stem cells, but its function in adult tenocytes is less well-defined. The aim of this study was to further define the role of Scx in mediating the adult tenocyte mechanoresponse.ResultsEquine tenocytes exposed to siRNA targeting Scx or a control siRNA were maintained under cyclic mechanical strain before being submitted for RNA-seq analysis. Focal adhesions and extracellular matrix-receptor interaction were among the top gene networks downregulated in Scx knockdown tenocytes. Correspondingly, tenocytes exposed to Scx siRNA were significantly softer, with longer vinculin-containing focal adhesions, and an impaired ability to migrate on soft surfaces. Other pathways affected by Scx knockdown included increased oxidative phosphorylation and diseases caused by endoplasmic reticular stress, pointing to a larger role for Scx in maintaining tenocyte homeostasis.ConclusionsOur study identifies several novel roles for Scx in adult tenocytes, which suggest that Scx facilitates mechanosensing by regulating the expression of several mechanosensitive focal adhesion proteins. Furthermore, we identified a number of other pathways and targets affected by Scx knockdown that have the potential to elucidate the role that tenocytes may play in the development of degenerative tendinopathy.

Activity-Induced Increase in Achilles Tendon Blood Flow Is Age and Sex Dependent

Background: Previous research of a young adult population identified a lower increase in Achilles tendon blood flow immediately after a running activity as a significant predictor for the development of Achilles tendinopathy (AT). Furthermore, advancing age is often mentioned as a risk factor for the development of AT, and the highest incidence for AT is reported to occur in middle-aged recreational male athletes. Purpose: To investigate the effect of age, sex, and type of physical activity on the increase in Achilles tendon blood flow. Study Design: Controlled laboratory study. Methods: Blood flow measurements of 33 subjects aged 18 to 25 years and 30 subjects aged 40 to 55 years were obtained before and after 4 physical activities performed in randomized order: running, cycling, dynamic stretching, and rope skipping. Blood flow measurements of the Achilles tendon were performed before, immediately after, 5 minutes after, and 10 minutes after the physical activities. The effect of age, sex, and physical activities on the increase in blood flow was investigated with linear mixed models. Results: The results of this study identified that running, rope skipping, and cycling resulted in a significant increase in tendon blood flow (P ≤ .001), whereas stretching did not. Prominent was the finding that the increase in blood flow after activity was significantly lower in the older population as compared with the younger population (P < .001). Furthermore, male participants in the older group showed a significantly lower increase in tendon blood flow than did their female counterparts (P = .019). Conclusion: This study identified that sex and age significantly influence the increase in blood flow after activity, possibly explaining the increased risk for AT among middle-aged recreational athletes. Clinical Relevance: This study possibly identified one of the mechanisms explaining why an older male population is at increased risk for developing AT. Given that the lower increase in blood flow is an identified risk factor according to previous research, preventative measures should focus on improving this blood flow during physical activity in the physically active older male population. Registration: NCT03218605 (ClinicalTrials.gov identifier).

Fc receptor-like 3 (\u2212169T>C) polymorphism increases the risk of tendinopathy in volleyball athletes: a case control study

BackgroundTendinopathy pathogenesis is associated with inflammation. Regulatory T (Treg) cells contribute to early tissue repair through an anti-inflammatory action, with the forkhead box P3 (FOXP3) transcription factor being essential for Treg function, and the FC-receptor-like 3 (FCRL3) possibly negatively regulating Treg function. FCRL3 –169T>C and FOXP3 –2383C>T polymorphisms are located near elements that regulate respective genes expression, thus it was deemed relevant to evaluate these polymorphisms as risk factors for tendinopathy development in athletes.MethodsThis case-control study included 271 volleyball athletes (146 tendinopathy cases and 125 controls) recruited from the Brazilian Volleyball Federation. Genotyping analyses were performed using TaqMan assays, and the association of the polymorphisms with tendinopathy evaluated by multivariate logistic regression.ResultsTendinopathy frequency was 63% patellar, 22% rotator cuff and 15% Achilles tendons respectively. Tendinopathy was more common in men (OR = 2.87; 95% CI = 1.67–4.93). Higher age (OR = 8.75; 95% CI = 4.33–17.69) and more years of volleyball practice (OR = 8.38; 95% CI = 3.56–19.73) were risk factors for tendinopathy. The FCRL3 –169T>C frequency was significantly different between cases and controls. After adjustment for potential confounding factors, the FCRL3 –169C polymorphism was associated with increased tendinopathy risk (OR = 1.44; 95% CI = 1.02–2.04), either considering athletes playing with tendon pain (OR = 1.98; 95% CI = 1.30–3.01) or unable to train due to pain (OR = 1.89; 95% CI = 1.01–3.53). The combined variant genotypes, FCRL3 –169TC or –169CC and FOXP3 –2383CT or –2383TT, were associated with an increased risk of tendinopathy among athletes with tendon pain (OR = 2.24; 95% CI: 1.14–4.40 and OR = 2.60; 95% CI: 1.11–6.10). The combined analysis of FCRL3 –169T>C and FOXP3 –2383C>T suggests a gene-gene interaction in the susceptibility to tendinopathy.ConclusionsFCRL3 –169C allele may increase the risk of developing tendinopathy, and together with knowledge of potential risk factors (age, gender and years playing) could be used to personalize elite athletes’ training or treatment in combination with other approaches, with the aim of minimizing pathology development risk.

Incidence of Achilles and Patellar Tendinopathy in Adolescent Elite Athletes

The study investigated the incidence of Achilles and patellar tendinopathy in adolescent elite athletes and non-athletic controls. Furthermore, predictive and associated factors for tendinopathy development were analyzed. The prospective study consisted of two measurement days (M1/M2) with an interval of 3.2±0.9 years. 157 athletes (12.1±0.7 years) and 25 controls (13.3±0.6 years) without Achilles/patellar tendinopathy were included at M1. Clinical and ultrasound examinations of both Achilles (AT) and patellar tendons (PT) were performed. Main outcome measures were incidence tendinopathy and structural intratendinous alterations (hypo-/hyperechogenicity, vascularization) at M2 [%]. Incidence of Achilles tendinopathy was 1% in athletes and 0% in controls. Patellar tendinopathy was more frequent in athletes (13%) than in controls (4%). Incidence of intratendinous alterations in ATs was 1-2% in athletes and 0% in controls, whereas in PTs it was 4-6% in both groups (p>0.05). Intratendinous alterations at M2 were associated with patellar tendinopathy in athletes (p≤0.01). Intratendinous alterations at M1, anthropometric data, training amount, sports or sex did not predict tendinopathy development (p>0.05). Incidence of tendinopathy and intratendinous alterations in adolescent athletes is low in ATs and more common in PTs. Development of intratendinous alterations in PT is associated with tendinopathy. However, predictive factors could not be identified.

MicroRNA 148a-3p promotes Thrombospondin-4 expression and enhances angiogenesis during tendinopathy development by inhibiting Krüppel-like factor 6

Tendinopathy is a common musculoskeletal disorder with characteristic hypervascularity. The mechanism of angiogenesis in tendinopathy remains unclear. The present study aimed to investigate the roles of miR-148a-3p in angiogenesis development of tendinopathy. In this study, we demonstrated that miR-148a-3p expression was increased in tendinopathy tissues and positively correlated with CD34 levels which is a specific marker for angiogenesis. We identified Krüppel-like factor 6 (KLF6) as a direct target gene of miR-148a-3p in tenocytes. Furthermore, reduced levels of KLF6 in tendinopathy tissues was showed using qRT-PCR and immunohistochemical analysis, compared with controls. A negative correlation between the levels of KLF6 mRNA and miR-148a-3p was observed. Then, we verified that miR-148a-3p could regulate Tsp-4 expression by targeting KLF6 in tenocyte and was positively correlated with Tsp-4 levels in tendinopathy tissues. In a coculture system of tenocytes with endothelial cells (ECs), we observed that transfection of Lv-miR-148a-3p markedly upregulated EC angiogenesis. In summary, our data establish a novel molecular mechanism by which miR-148a-3p upregulates Tsp-4 expression in tenocytes to promote EC angiogenesis by targeting KLF6, which could be helpful for the treatment of tendinopathy in the future.

Psoriasis and the risk of foot and ankle tendinopathy or enthesopathy in the absence of psoriatic arthritis: a population-based study

ObjectivesImaging studies in patients with cutaneous psoriasis have demonstrated asymptomatic bone and tendon changes, commonly of the foot and ankle. We sought to determine if patients with cutaneous psoriasis have...

Quantitative Analysis of Patellar Tendon Abnormality in Asymptomatic Professional “Pallapugno” Players: A Texture-Based Ultrasound Approach

Abnormalities in B-mode ultrasound images of the patellar tendon often take place in asymptomatic athletes but it is still not clear if these modifications forego or can predict the development of tendinopathy. Subclinical tendinopathy can be arbitrarily defined as either (1) the presence of light structural changes in B-mode ultrasound images in association with mild neovascularization (determined with Power Doppler images) or (2) the presence of moderate/severe structural changes with or without neovascularization. Up to now, the structural changes and neovascularization of the tendon are evaluated qualitatively by visual inspection of ultrasound images. The aim of this study is to investigate the capability of a quantitative texture-based approach to determine tendon abnormality of “pallapugno” players. B-mode ultrasound images of the patellar tendon were acquired in 14 players and quantitative texture parameters were calculated within a Region of Interest (ROI) of both the non-dominant and the dominant tendon. A total of 90 features were calculated for each ROI, including 6 first-order descriptors, 24 Haralick features, and 60 higher-order spectra and entropy features. These features on the dominant and non-dominant side were used to perform a multivariate linear regression analysis (MANOVA) and our results show that the descriptors can be effectively used to determine tendon abnormality and, more importantly, the occurrence of subclinical tendinopathy.

Global Epidemiological Analysis of Prevalence and Risk Factors Associated With the Deep Digital Flexor Tendinopathy in the Equine Distal Limb: 100 Cases

The purpose of this study was to establish the prevalence and the risk factors for deep digital flexor (DDF) distal tendinopathy in the equine limb (from the proximal extremity of the middle phalanx to the insertion of this tendon to the distal phalanx) and to identify the circumstances that promote this pathological condition. This epidemiological analysis was performed on 100 horses diagnosed with DDF distal tendinopathies at CIRALE-Hippolia between January 2009 and June 2010. All horses included in this study were diagnosed by ultrasonographic examination with front limb lameness associated with distal DDF tendinopathies at CIRALE-Hippolia in the aforementioned period. The sources of information were the individual medical records of horses. The considered risk factors were as follows: breed, age, sex, and athletic discipline. The risk was quantified by analyzing statistical association of the studied condition and different factors that can interfere with its evolution. Lameness associated with distal DDF tendinopathy has been mostly identified in jumping horses. The most well represented age category was the 8–10 years one, but the horses aged between 11 and 14 years had the highest risk for developing DDF tendinopathy. Females were more prone to this type of injury. The current epidemiological analysis provides a model for risk and protective factors for the development of DDF tendinopathy in the equine distal limb. The most susceptible group of equids are female Warmbloods more than the age of seven, whereas young male Thoroughbreds and French Trotters (0–3 year-old) carry the lowest risk in developing this pathology.