Les tendinopathies sont fréquentes et entraînent une diminution de la qualité de la vie à long terme. Les connaissances des événements physiopathologiques suivant un traumatisme tendineux sont toutefois parcimonieuses. Conséquemment, peu ou pas de stratégies thérapeutiques permettent d’en accélérer le processus de réparation. Le but de cette thèse était donc d’explorer les mécanismes cellulaires et le rôle de différents régulateurs potentiels de la réaction inflammatoire dans la réparation des tendons. Dans un premier temps, nous avons mis au point un modèle de blessure tendineuse aiguë consistant en l’injection de collagénase dans le tendon d’Achille de rats. Nous avons observé, par marquages immunohistochimiques, que les neutrophiles étaient les premières cellules à infiltrer le site de la lésion, suivis des macrophages. Nous avons également remarqué, dans un second projet que l’injection de collagénase, une métalloprotéinase, dans le tendon, induisait une altération des propriétés mécaniques des tendons de rats, et que l’administration d’un anti-inflammatoire non stéroïdien n’affectait pas significativement cette perte fonctionnelle, probablement en raison d’un effet anti-inflammatoire localisé en périphérie des faisceaux tendineux. En utilisant le même modèle expérimental, nous avons ensuite étudié le rôle d’un médiateur central de la physiopathologie tendineuse : p53. L’inhibition pharmacologique de la transactivation des gènes cibles de p53, par une molécule appelée pifithrin-α, a diminué l’accumulation des cellules inflammatoires dans le tendon blessé. Cet effet anti-inflammatoire n’était pas associé à une diminution de la perte fonctionnelle en phase aiguë, mais retardait la guérison de la blessure tendineuse. Puisque les stratégies anti-inflammatoires ne diminuent pas le déficit fonctionnel en phase inflammatoire, nous avons finalement testé le dogme voulant que les cellules inflammatoires pouvaient causer des dommages non spécifiques à la matrice des tendons. L’injection intra tendineuse de carraghénine a induit une accumulation massive de cellules inflammatoires. Cependant, cette réaction n’était pas associée à une altération des propriétés biomécaniques ni à une diminution du contenu en collagène des tendons. En conclusion, nos résultats ont permis d’accroître les connaissances de la séquence physiopathologique suivant un traumatisme tendineux et jettent un doute sur les effets délétères de l’inflammation suivant un traumatisme aigu. / Tendinopathies show a high prevalence and can alter the quality of life for many years. Nevertheless, the pathophysiology of tendinopathies is not well characterized and it may explain the lack of effective treatments to accelerate tendon healing. This thesis was therefore dedicated to the study the role of potential regulators of the pathophysiological sequence following tendon trauma. In a first project we set up an experimental model of acute tendon injury where collagenase was injected into the Achilles tendon of rats. This procedure induces a classical sequence of accumulation of leukocytes where neutrophils accumulate massively 24 hours following the injection of collagenase, followed by macrophages on day 3. We also showed, in a second project, that injection of collagenase reduces the load to failure by more than 50% 3 days post trauma. Moreover, administration of diclofenac, a non-steroidal anti-inflammatory drug, did not rescue tendons from that loss of mechanical strength, presumably because the anti-inflammatory effect was located in the paratenon and not in the core of the tendon where the load-resisting collagen bundles are located. In a third project we studied the role of p53, a putative regulator of the inflammatory process and extracellular matrix homeostasis, on the pathophysiological sequence following an acute tendon trauma. Transactivation inhibition of p53 reduced the accumulation of neutrophils and macrophages in the entire tendon. This anti-inflammatory effect was not associated to a rescue of the mechanical properties and even delayed the onset of healing. In view of the evidence that anti-inflammatory strategies failed to rescue tendons from functional loss, we challenged the dogma that the inflammatory process could induce non-specific damages to the tendon extracellular matrix. Intra-tendinous injection of carrageenan induced a massive accumulation of inflammatory cells. However this was neither associated to a reduction of tendons’ collagen content nor to a reduction of the load to failure. In conclusion, we identified new mediators and mechanisms of the pathophysiology of tendons. Our results challenge the concept that inflammatory cells strictly play deleterious effects following tendon trauma.

INTRODUCTION : La tendinopathie de la coiffe des rotateurs (CR) entraîne de la douleur et des limitations fonctionnelles qui seraient expliquées en partie par une perturbation du contrôle neuromusculaire de l’épaule. L’entrainement sensorimoteur a été démontré efficace pour rééduquer le contrôle neuromusculaire suite à cette atteinte. Chez des populations neurologiques, l’ajout de stimulation anodale transcrânienne par courant direct (a-tDCS) à un entrainement sensorimoteur permet d’améliorer plus rapidement la condition des patients. Ainsi, l’ajout de l’a-tDCS pourrait optimiser l’efficacité de l’entrainement sensorimoteur à la suite d’une tendinopathie de la CR. OBJECTIF : Comparer un groupe recevant un programme de réadaptation centré sur l’entrainement sensorimoteur et l’a-tDCS, à un groupe recevant le même programme mais avec une a-tDCS placébo. MÉTHODOLOGIE : Quarante adultes présentant une tendinopathie de la CR ont pris part aux 4 évaluations (0, 3, 6, 12 semaines) et au programme de réadaptation de 6 semaines (incluant éducation, entrainement sensorimoteur et renforcement musculaire) de cet essai clinique randomisé à triple insu (participants, physiothérapeute traitant, évaluateur). Les symptômes et limitations fonctionnelles (questionnaires Disability of the Arm, Shoulder and Hand [DASH] et Western Ontario Rotator Cuff [WORC]) et la distance acromiohumérale (DAH ; mesures échographiques à 0°, 45°, 60° d’élévation du bras) étaient les variables à l’étude. L’a-tDCS était positionnée au-dessus du cortex moteur controlatéral à la douleur (stimulation 1,5 mA pour 30 minutes) et appliquée pendant l’entrainement sensorimoteur. RÉSULTATS : Une amélioration statistiquement significative aux DASH et WORC à 3, 6 et 12 semaines et de la DAH à 45° et 60° à 6 semaines chez les deux groupes a été démontrée (effet Temps P < 0,05). Toutefois, aucune différence entre les groupes n’a été observée dans cette amélioration pour toutes les variables (interaction Groupe X Temps P > 0,43) CONCLUSION : L’ajout de l’a-tDCS ne semble pas améliorer l’efficacité de l’entrainement sensorimoteur pour les personnes atteintes d’une tendinopathie de de la CR. / BACKGROUND: Rotator cuff (RC) tendinopathy results in pain and functional limitations, and these deficits can be explained, in part, by an alteration of shoulder motor control. For treatment of RC tendinopathy, sensorimotor training has been shown to be effective to reduce symptoms and improve function, as well as optimize shoulder motor control. Anodal transcranial direct current stimulation (a-tDCS), an electrostimulation technique known to modulate the motor cortex excitability, has been shown to enhance the effects of sensorimotor training in neurological populations. The addition of a-tDCS during a rehabilitation program centered on sensorimotor training could enhance motor learning associated with sensorimotor training and thus improve treatment outcome. OBJECTIVE: To compare a group receiving a rehabilitation program centered on sensorimotor training with a-tDCS to a group receiving the same rehabilitation program with sham a-tDCS. METHODS: Forty adults with RC tendinopathy part in the 4 evaluation sessions (0, 3, 6, 12 weeks) and the 8 supervised physiotherapy treatments during the 6-week rehabilitation program (education, sensorimotor training, strengthening) of this triple-blind randomized control trial (evaluator, physiotherapist and participants). Outcome measures were symptoms and functional limitations (Disability of the Arm, Shoulder and Hand [DASH] and the Western Ontario Rotator Cuff [WORC] index), as well as acromiohumeral distance (AHD; ultrasonographic measurement at 0° and 60° of elevation arm). A-tDCS (1.5 mA for 30 minutes) was applied during sensorimotor training on the motor cortex contralateral to the side of pain. RESULTS: Both groups showed significant improvement in DASH and WORC at 3, 6 and 12 weeks and in AHD at 45° and 60° at 6 weeks (P < .05). However, no significant Group-by-Time interaction was observed for all outcomes (P > .43). CONCLUSION: Results do not demonstrate any added effects of a-tDCS during a rehabilitation program in individuals with RC tendinopathy.

The diploma thesis deals with the design of the supporting structure of a road bridge over a reservoir. Two variants of bridging were processed. The selected variant is a three span continuous beam. It is made of box girder cross section with a variable height. The structure has a total length of 156,8 m and is built using balanced cantilever method. The bridge is designed and assessed according to the limit states for temporary and permanent design situations. Structural analysis, drawing documentation and visualization of the bridge is part of the work.

Este estudo avaliou a efetividade de uma nova membrana bioabsorvível com propriedades mecânicas e químicas mais adequadas para o uso em tendões. A avaliação foi realizada em coelhos submetidos a reconstrução da porção gastrocnêmia do tendão calcâneo. Foi feita uma avaliação prévia das propriedades mecânicas da membrana com uso de dinamômetro digital que demonstrou capacidade de deformação elástica mínima de 100%. Todos os coelhos foram submetidos a tenotomia e reparo da porção gastrocnêmia do tendão direito, após isso foram randomicamente separados em grupos envelopado com membrana e controle. A extração foi realizada nos seguintes períodos: sete, 14 e 28 dias. A avaliação foi realizada através da macroscopia, histologia, mensuração objetiva do colágeno à luz polarizada pelo image-J®, mensuração de glicosaminoglicanos sulfatados e expressão gênica de proteoglicanos. Na avaliação macroscópica o grupo com membrana apresentou menos aderência e melhor direcionamento das fibras e tecido mais homogêneo em 14 e 28 dias, p=0,02 e 0,03 respectivamente. Na histologia a Classificação de Watkins modificada apresentou as seguintes médias: 14,67±0,42 membrana e 12,67±0,56 sem membrana, p=0,03 em 14 dias, e 19,88±0,83 membrana e 17,25±0,62 sem membrana, p=0,02 em 28 dias. Na mensuração do colágeno as médias dos valores de cinza(mvc) o colágeno tipo III foram de 17,97±1,83 membrana e 12,63±1,07 sem membrana p=0,03 em 14 dias. Para o colágeno tipo I as médias foram de 2,41±0,33mvc membrana e 1,31±0,18mvc sem membrana p=0,01 em 14 dias e 7,30±0,63mvc membrana e 2,92±0,32mvc sem membrana p < 0,0001 em 28 dias. A média dos GAGs foi avaliada em três porções do tendão, proximal, central e distal, em ug/mg de tecido seco. Em sete dias apresentou diferença significativa apenas na porção distal 0,80±0,04 com e 0,38±0,04 sem membrana para condroitin-sulfato em 14 dias não apresentou diferenças entre os grupos. O dermatan-sulfato apresentou diferença estatisticamente significante em 7 dias apenas na porção central 0,42±0,09 com membrana e 1,29±0,67 sem membrana p=0,02. Em 14 dias não foram observadas diferenças entre os grupos. Houve grande variabilidade na expressão gênica no teste das amostras com beta-Actina e GAPDH levando a resultados inconclusivos ou não variação entre os grupos que pode sugerir não variabilidade na expressão gênica dos GAGs no período de 28 dias. Os dados fornecidos por esse trabalho mostram que a envelopagem com a membrana bioabsorvível promoveu aceleração dos processos cicatriciais da porção gastrocnêmia do tendão calcâneo de coelhos / This study assessed the effectiveness of a new absorbable membrane, that presents mechanical and chemical features more suitable to tendons, in rabbit tendons. Before the animal model assessments a mechanical study of the membrane was carried out demonstrating that the minimal capability for elastic deformation of the membrane was more than 100%. All rabbits underwent to tenotomy and reconstruction of the right gastrocnius tendons, thereafter they were randomly divided in tendon wrapped by the membrane and control groups. Extraction was performed in the following periods of time: seven, 14 and 28 days. Assessments used macroscopy, histology, objective collagen assessment by using polarized light and Image-J® program in mean of gray values(mgv), sulphated glycosaminoglycans, genetic expression of proteoglycans. In the macroscopic 14 and 21-day assessments the membrane group presented less adherences p=0.02 and p=0.03 respectively. The modified Watkins classification: 14,67±0,42 membrane and 12,67±0,56 without membrane p=0,03 for 14 days; 19,88±0,83 membrane and 17,25±0,62 without membrane p=0,02 for 28 days. The type III collagen were 17,97±1,83 membrane and 12,63±1,07 without membrane p=0,029 for 14 days. For type I collagen were 2,41±0,33 membrane and 1,31±0,18 without membrane p=0,01 for 14 days and 7,30±0,63 memebrane and 2,92±0,32 without membrane p < 0,0001 for 28 days. The glycosaminoglycans were measured in 3 tendon portions, distal, central and proximal, by using ug/mg of dry tissue. In seven days just the distal part presented statistical differences 0,80±0,04 membrane and 0,38±0,04 without membrane, for 14 days no differences were found for Chondroitin-Sulphate. For Dermatan-Sulphate the central part of the tendon 0,42±0,09 and 1,29±0,67 p=0,02, for 14 days no differences were found. There was high variability for beta-actin and GAPDH for the samples in 28 days with inconclusive results that may mean no variability in gene expression of GAGs at this time period. Results as mentioned above demonstrated that the wrapped tendons by the new membrane presented acceleration in the healing processes for gastrocnemius tendons of New Zealand Rabbits

As patologias apresentadas por algumas estruturas e a necessidade de aumento da capacidade de carga de outras fizeram com que diversas técnicas fossem desenvolvidas para o reforço de vigas de concreto armado. Uma delas é a incorporação e protensão de cabos externos. O grande diferencial desta técnica quando comparada às demais é o seu caráter ativo. Ou seja, por meio da protensão é possível aplicar forças de forma a diminuir o nível de tensões atuantes sobre a estrutura. Neste trabalho, é apresentado um amplo estado-da-arte sobre este tipo de reforço. São descritas algumas obras realizadas com esta técnica e relatados e analisados alguns ensaios em vigas protendidas com cabos externos. Diversos métodos de cálculo de vigas protendidas com cabos não aderentes são apresentados. É mostrado, também, um procedimento para previsão da forma de ruína de vigas protendidas com cabos externos. Foi feito um estudo experimental, ensaiando-se 3 vigas de concreto armado reforçadas por meio da protensão de cordoalhas engraxadas. Os resultados dos ensaios são analisados e comparados com previsões teóricas feitas a partir dos métodos de cálculo estudados e com resultados de ensaios em vigas reforçadas com outras técnicas. Do estudo realizado, foi possível comprovar os benefícios da protensão não só no que se refere à resistência ao momento fletor, mas também ao esforço cortante. / Many techniques for concrete beams strengthening have been developed along the years. Among them, prestressing of external tendons, which presents a major difference when compared to the others: controlled forces can be applied to reduce undesirable stresses in the structure. This work presents a state-of-the-art review on this technique. Some methods proposed to estimate the flexural capacity of beams prestressed with unbonded tendons are reviewed. It is also shown a procedure to predict the failure mode of the beams. Three reinforced concrete beams were strengthened by prestressing of external strands and tested. Results are analyzed and compared with both theoretical predictions and other test results of beams strengthened by alternative techniques. From the research, the benefits of prestressing on improving the flexural capacity and the shear strength of reinforced concrete beams could be confirmed.

In summary, the biomechanical stimulations can augment osteotendinous healing processes by facilitating better fibrocartilagious transitional zone regeneration as well as the restoration of proprioceptions, and the early application showed the more beneficial effects. However, further experimental and clinical studies are still needed to explore the optimal timing, intensity, frequency, and duration of the proposed postoperative biomechanical stimulation protocols. / LIPUS is a "non-contact" biomechanical stimulation, which can provide a direct mechanical stimulation through cavitation and acoustic microstreaming effects to improve tissue healing in a less-than-rigid biomechanical environment. So the mechanical stimulation induced from LIPUS could be applied immediately after surgery without worrying about the mechanical strain exceed the structural property at the osteotendinous healing interface in the early phase of repair. In this part of study, we also examined the effects of the regime of biomechanical stimulations applying immediately after repair on the osteotendinous healing interface. By using the same healing junction model, forty-two female New Zealand white rabbits were randomly divided into two groups; daily mechanical stimulation was applied immediately after surgery lasting up to post-operative 12 weeks on the healing interface in the treatment group. The regime of mechanical stimulations included by LIPUS was 20 minutes, 5 days per week for 4 weeks, followed by cyclic mechanical stimulation generated from quadriceps muscles induced by FES for 8 weeks. Results showed that early application of biomechanical stimulations on the osteotendinous healing interface were significantly better radiologically, histologically and biomechanically than that of not any or later application of the biomechanical stimulations during the osteotendinous healing processes when assessing at the same healing time point. In addition, the early application of biomechanical stimulations showed the better functional recovery in terms of the restoration of the proprioceptions, which an increased numbers of sensory nerve endings labeled by calcitonin gene-relate peptide (CGRP) was detected in the whole osteotendinous healing complex. / Sports or trauma injuries around osteotendinous junctions are common; treatments usually require surgical reattachment of the involved tendon to bone. Restoration of osteotendinous junction after repair is slow and difficult due to regenerating the intermitted fibrocartilage zone to connect two different characteristic tissues, tendon to bone. Although the factors influencing fibrocartilage zone regeneration and remodeling during osteotendinous repair are poorly understood, however, is believed that the mechanical environment plays an important role in such healing process. In present study, the effects of mechanical stimulation on osteotendinous healing process were examined, in the way of mechanical stimulations induced by biophysical stimulations, surface functional electric stimulation (FES) and low intensity pulsed ultrasound (LIPUS), applying on the patellar tendon to patellar bone healing interface in an established partial patellectomy model in rabbits. / The mechanotransductive stimulation linked to the transmission of forces across osteotendinous junction can be generated from its muscle contraction induced by FES. In the partial patellectomy model, thirty-five female New Zealand white rabbits were randomly divided into two groups with initial immobilization for 6 weeks, daily FES was applied to quadriceps muscles for 30 minutes, 5 days per week for 6 weeks in treatment group and compared with non-treatment control group at postoperative week 6, 12 and 18, radiologically, histologically and biomechanically. Results showed that FES-induced cyclic mechanical stimulation significantly increased new bone formation and its bone mineral density. An elevated expression of tenascin C and TGFbeta1; an increased proteoglycant stainability; mature fibrocartilage zone formation with better resumptions of biomechanical properties also observed on the osteotendinous healing interface, indicating that the post-operative programmed cyclic mechanical stimulation generated from its muscle contraction has beneficial effects on osteotendinous healing processes by facilitating the fibrocartilagious transitional zone regeneration. / by Wang Wen. / Advisers: Kai Ming Chan; Ling Qin. / Source: Dissertation Abstracts International, Volume: 68-03, Section: B, page: 1550. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references (p. 159-175). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.

Establishment of animal model for studying treatment efficacy of low-intensity pulsed ultrasound stimulations for accelerating bone-tendon repair. Standard partial patellectomy was conducted in the 18-week old rabbits that were then divided into the LIPUS treatment and control groups. The animals were followed for 2, 4, 8, and 16 weeks for various tissue analyses. LIPUS was applied to the experimental animals from postoperative day 3 to 16 weeks. We demonstrated that the healing process of PPT junction was initiated through endochondral ossification. The results showed that the size and length of newly formed bone, and its bone mineral content (BMC), but not its bone mineral density (BMD) were correlated with the failure load, ultimate strength and energy at failure. Using radiographic, biomechanical, histomorphologic and biomechanical methods, it was found that LIPUS had significant accelerating effect on PPT junction repair. We validated our study hypothesis in that LIPUS enhances bone-tendon junction healing by stimulating angiogenesis, chondrogenesis and osteogenesis. / Establishment of in vitro model for mechanism study on effects of low-intensity pulsed ultrasound stimulations. An in vitro model of osteoblast-like cell line (SaOS-2 cells) was studied using cDNA microarray to explore the molecular mechanism mediated by LIPUS. This microarray analysis revealed a total of 165 genes that were regulated at 4 and 24 hours by LIPUS treatment in osteoblastic-like cells. These genes belonged to more than ten protein families based on their function and were involved in some signal transduction pathways. This study has validated the hypothesis that LIPUS can regulate a number of critical genes transient expressions in osteoblast cell line Saos-2. / Keywords. partial patellectomy model; bone-tendon junction repair; low intensity pulsed ultrasound stimulations (LIPUS); gene expression; complementary DNA microarray; rabbit. / This study explored the intact morphology, regular healing and the augmented healing under the effects of low intensity pulsed ultrasound stimulations (LIPUS) on the patella-patella tendon (PPT) junction in a rabbit partial patellectomy model. To probe its possible mechanism, the key genes involved in regulating osteogenesis mediated by LIPUS were identified using the state-of-the-art methods---complementary DNA microarray. / Lu Hongbin. / "June 2006." / Advisers: Ling Qin; Kwok Sui Leung. / Source: Dissertation Abstracts International, Volume: 68-03, Section: B, page: 1548. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references (p. 259-288). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.

Ligament/tendon tissue engineering has the potential to provide therapies that overcome the limitations of incomplete natural healing responses and inadequate graft materials. While ligament/tendon fibroblasts are an obvious choice of cell type for these applications, difficulties associated with finding a suitable cell source have limited their utility. Mesenchymal stem cells/marrow stromal cells (MSCs) are seen as a viable alternative since they can be harvested through routine medical procedures and can be differentiated toward a ligament/tendon fibroblast lineage. Further study is needed to create an optimal biomaterial/biomechanical environment for ligament/tendon fibroblastic differentiation of MSCs. The overall goal of this dissertation was to improve the understanding of the role that biomechanical stimulation and the biomaterial environment play, both independently and combined, on human MSC (hMSC) differentiation toward a ligament/tendon fibroblast phenotype. Specifically, the effects of cyclic tensile stimuli were studied in a biomaterial environment that provided controlled presentation of biological moieties. The influence of an enzymatically-degradable biomaterial environment on hMSC differentiation was investigated by creating biomaterials containing enzymatically-cleavable moieties. The role that preculture may play in tensile responses of hMSCs was also explored. Together, these studies provided insights into the contributions of the biomaterial and biomechanical environment to hMSC differentiation toward a ligament/tendon fibroblast phenotype.

Le tendon est un organe impliqué dans de nombreux troubles musculo squelettiques. Les connaissances des différentes molécules impliquées dans la biologie des tendons permettent d'envisager des traitements par thérapie génique. L'objectif de cette thèse a été d'évaluer la faisabilité de transférer des gènes dans les tendons par deux méthodes non virales : une méthode chimique utilisant des nanoparticules de silice mésoporeuses et une méthode physique reposant sur l'utilisation des ultrasons et des microbulles de gaz (sonoporation). Dans une première étude, nous avons montré que des nanoparticules de silice mésoporeuses sont capables de transférer efficacement des gènes dans le tendon d'Achille de rat. Celles-ci ont été utilisées pour transférer le gène du facteur de croissance PDGF dans des tendons lésés. Nos résultats indiquent une accélération de la réparation du tendon lésé. Dans une deuxième étude, nous avons utilisé la sonoporation, technique jamais appliquée aux tendons. Nous avons déterminé les paramètres acoustiques permettant un transfert de gènes efficace dans le tendon d'Achille de souris. Une expression stable d'un transgène a été maintenue pendant 100 jours suite à une injection locale d'ADN en présence de microbulles de gaz. Nous avons ensuite utilisé cette méthode dans un modèle de souris transgénique invalidée pour le gène de la fibromoduline possédant des fibres de collagène anormales. Une restauration remarquable du phénotype de ces souris a été observée suite au transfert du gène de la fibromoduline. Nous avons ensuite étudié les interactions entre les microbulles, la membrane plasmique et le transfert de gènes dans les cellules sous ultrasons. Ces études ont permis d'identifier pour la première fois, une pénétration des microbulles de gaz dans la cellule et un trafic intracellulaire de l'ADN impliquant la voie d'endocytose clathrine dépendante. En conclusion, les deux méthodes de transfert de gènes non virales ont permis de transfecter des gènes efficacement dans les tendons. Ces résultats prometteurs permettent d'envisager leur exploitation pour des applications thérapeutiques dans les pathologies tendineuses.

Tendonopathy, resulting in the loss of mechanical strength of a tendon, is a serious health problem affecting many people. The common symptom of tendonopathy is pain – patients' daily activities, their participation in sport and exercise, and their ability to work are greatly compromised. Tendonopathy is considered to be a degenerative disorder caused by repetitive injury of the tendon. The most common tendon lesions are Achilles tendon rupture, lateral epicondylitis (tennis elbow) and rotator cuff tear. However, in spite of its clinical significance, our knowledge about tendonopathy is still very poor. This research was undertaken to investigate the pathology of tendonopathy. It is proposed that apoptosis, autophagic cell death and myofibroblasts play a role in the progression of tendonopathy in the rotator cuff; the aim of this study was therefore to determine if this was indeed the case. Tendon tissues were collected from 30 patients suffering from rotator cuff tears. A terminal deoxynucleotidyl transferase biotin-dUTP nick end labelling (TUNEL assay) was performed to detect apoptosis. Autophagic cell death of the tenocytes in the ruptured rotator cuff tendon was detected by immunohistochemical staining for ubiquitin. Myofibroblasts were identified immunohistochemically with anti-alpha-smooth muscle actin (anti--SMA) antibody. The distribution of apoptosis, autophagic cell death and myofibroblasts, as well as the total cell density, were assessed respectively and were correlated using a four-category (i.e. graded from 0-3) degeneration of collagen matrix. – 6 – The results showed that apoptosis, autophagic cell death and myofibroblasts were observed in all of the samples. The highest percentage of autophagic cell death was evidenced in the Grade 2 matrix, while the percentage of apoptosis increased significantly with the increase of matrix degeneration from Grade 0-3; a similar pattern was found for myofibroblasts. The total cell numbers varied among the matrix grades, with the maximum and minimum percentages occurring in Grades 1 and 3, respectively. It can be concluded that apoptosis, autophagic cell death and myofibroblasts might be closely related to the damage of the extracellular matrix (ECM) structure.