INTRODUÇÃO: A disfunção do tendão tibial posterior (DTTP), principal causa de pé plano adquirido no adulto, é mais frequente em indivíduos do gênero feminino e apresenta pico de incidência na sexta década de vida. Diversos fatores de risco - intrínsecos e extrínsecos - e condições sistêmicas associadas são descritas na literatura. A predisposição genética resultante da maior expressão de genes relacionados ao metabolismo hormonal, principalmente do estrogênio, pode desempenhar influência na fisiopatogenia dessa lesão em associação aos fatores comportamentais e endógenos. OBJETIVO: Analisar a frequência de polimorfismos nos genes dos receptores de estrogênio (RE) dos tipos alfa (RE1) e beta (RE2), em pacientes na pós-menopausa com diagnóstico de tendinopatia do tendão do músculo tibial posterior e em pacientes assintomáticas. CASUÍSTICAS e MÉTODOS: Foram incluídas 202 pacientes do gênero feminino (N=202), com idade superior a 40 anos, divididas em 2 grupos (n=101), de casos e controles. Foram definidos como casos pacientes na pós-menopausa com diagnóstico de DTTP, realizado por meio dos exames clínico e de imagem (RM), e, como controles, pacientes com as mesmas características epidemiológicas, assintomáticas, que apresentavam exames clínico e de imagem normais para a avaliação do tendão tibial posterior. Células epiteliais da mucosa bucal das pacientes incluídas no estudo foram coletadas por meio de bochecho com solução glicosada para extração e análise do RESULTADOS: Pacientes portadoras do genótipo xx do SNP XbaI apresentaram risco estimado 2,38 vezes maior (p = 0,029) de desenvolver a DTTP quando comparadas às portadoras dos genótipos selvagem ou heterozigoto. Já a distribuição dos genótipos dos SNP PvuII e AluI não apresentou associação com o desenvolvimento da doença. ADN genômico. Os SNP dos genes dos RE1 (XbaI e PvuII) e RE2 (AluI) foram avaliados com base em PCR-RFLP. CONCLUSÃO: O presente estudo demonstra que pacientes com polimorfismo XbaI do RE1 apresentam maior risco de desenvolvimento da disfunção do tendão tibial posterior / INTRODUCTION: Posterior tibial tendon dysfunction (PTTD), the most common cause of flatfoot deformity in adults, is more frequent in the female gender with peak incidence in the sixth decade of life. Multiple risk factors - intrinsic and extrinsic - and associated systemic conditions have been described in the literature. Genetic predisposition secondary to hyperexpression of genes related to hormonal metabolism, particularly the estrogens, may play a role in the pathogenesis of this disease acting in association with behavioral and endogenous risk factors. OBJECTIVE: The aim of this study was to analyze the frequency of polymorphisms of the estrogen receptors (ER) alpha (ER1) and beta (ER2) in postmenopausal women with PTTD when compared to asymptomatic control patients. METHODS: 202 female patients over the age of 40 were included in the study (N = 202). They were then divided into 2 different groups (n = 101): cases and controls. We defined as cases postmenopausal women with symptomatic PTTD, diagnosed by clinical and MRI examinations. Females with similar epidemiology, but clinically asymptomatic and with normal MRI evaluation for the posterior tibial tendon were defined as controls. Oral mucosa epithelial cells were collected from the patients and genomic DNA was extracted from the samples. The SNPs for the ER1 (XbaI and PvuII) and ER2 (AluI) genes were assessed by PCR-RFLP. RESULTS: Patients with SNP Xbal genotype xx had 2.38 higher estimated risk (p = 0,029) in developing PTTD, when compared to patients with the other genotypes. No associations were found for the SNP PvuII and AluI. CONCLUSION: The present study demonstrates that patients with the Xbal single nucleotide polymorphism of estrogen receptor 1 gene have higher risk of developing posterior tibial tendon dysfunction

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.

Tissue, in particular its mechanical properties, is of interest from a material science point of view. The collagen fiber framework found in nearly all tissue forms the basis for the tissue's behavior. Connective tissue provides more interesting behavior, designed to bear significant load in one direction, while retaining the ability to stretch in other directions. Contributing factors to such behavior are fiber diameter and orientation. Small angle scattering analysis has been developed over the past century. Particular attention has been paid to x-ray and neutron scattering, both of which characterize features on a nanometer scale. Small angle light scattering (SALS) has the ability to characterize features on a micron scale, and is thus suitable for the analysis of collage fibers. Scattering data from several tendons were analyzed using the Generalized Indirect Fourier Transform (GIFT) program developed by Dr. Otto Glatter. The data is fit using cubic B-splines, and transformed into a probability density distribution function (abbreviated PDDF or p(r)). The PDDF can then be interpreted to give an average fiber diameter, as well as other structural information. Since this type of analysis has never been performed on collagen fibers, emphasis was placed on validating small angle light scattering as an appropriate technique to characterize collagen fiber diameter. This was accomplished by comparing the results with optical microscopy. Results from SALS analysis agree with features observed by optical microscopy. Small angle light scattering analysis is able to provide an analysis of structures superior to that of optical microscopy. Small angle scatter theory provides a three dimensional analysis of the structure. On the other hand, optical microscopy provides only a two dimensional view of the sample. The structure of collagen fibers in tissue is certainly three dimensional, making small angle light scattering a more suitable technique for characterization.

ACL injuries are ubiquitous and the literature surrounding ACL reconstructions is complex and difficult to comprehend. In summary, this paper provides a simple yet coherent overview of ACL injuries. Etiology, prevention, and the consequences of injury are discussed. The paper examines literature surrounding the decision to reconstruct the anterior cruciate ligament. An overwhelming quantity of literature is in favor of an ACL reconstruction in order to maintain an active lifestyle. ACL surgery has advanced exponentially in recent years and there is a multitude of fixation and tunneling methods. Graft choice for an ACL reconstruction is also complicated and multifactorial. In general, three types of grafts exist: autografts, allografts, and synthetic grafts. Autografts usually include the hamstring tendon (HT) and patella tendon (BTB), however, recent studies suggest the quadricep tendon (QT) may be a suitable graft. The BTB is often considered the “gold standard” due to its strength and stability. On the other hand, the HT is often used as it is less invasive and is associated with less antero-patellar knee pain. Common allografts include the patella tendon, Achilles tendon, and tibialis muscle group. Despite a higher cost, allografts are usually used in revision surgeries and leave patients with less donor-site morbidity. Lastly, synthetic grafts are growing in popularity, especially the LARS procedure, however, more research is needed. Lastly, this paper attempts to consolidate literature surrounding the QT graft. Only one meta-analysis focusing on the QT has been published, however, the last meta-analysis is from three years ago and several new studies have been published since. The recent literature suggests the QT is a viable option in terms of stability and functional outcomes. Specifically, when comparing the QT to BTB and HT, the QT grades similarity in KT-1000 scores, a common measure of knee laxity and stability. Additionally, IKDC scores, frequently used to assess functionality, show positive results. More literature is needed to fully understand the QT; however, preliminary research indicates the QT can be an esteemed option in ACL reconstruction surgery.

O objetivo deste estudo foi avaliar o efeito de diferentes tempos de tratamento do ultrassom terapêutico na cicatrização de lesão tendínea. Quarenta ratos machos Wistar (300 ± 45g), dos quais 32 sofreram tenotomia do tendão do calcâneo, foram divididos em 5 grupos: grupo C, sem tenotomia e tratamento, grupo T, com tenotomia e sem tratamento, US1,US2 e US3 submetidos à tenotomia e tratados com UST nos tempos de 1, 2 e 3 minutos por área de transdutor. Os animais foram mortos no 12º dia pósoperatório e os tendões retirados cirurgicamente para análise da organização das fibras colágenas utilizou-se o método de birrefringência (retardo óptico - OR). As fibras colágenas mostraram melhor agregação e organização no grupo US3 quando comparado ao grupo T (p<0.05). Concluise que o UST, aplicado no tempo de 3 minutos por área tratada, melhorou a organização das fibras colágenas no reparo tecidual de tendões de ratos / The aim of this study was to evaluate the effects of different treatment times of therapeutic ultrasound (US) on tendon injury healing. Forty male Wistar rats were selected (300 ± 45g) and 32, who underwent tenotomy of the Achilles tendon, were divided into five groups: Control, without tenotomy nor any treatment; tenotomy group, with tenotomy and without treatment; US groups (US1, US2, and US3), submitted to tenotomy and treated respectively with US for one, two, and three minutes per area of the transducer. The animals were sacrificed on the 12th post-operative day and the tendons were surgically removed for analyses of the collagen fiber organization by means of birefringence analyses, or optical retard. The collagen fibers showed better aggregation and organization in the US3 group, compared to the tenotomy group (p<0.05). The findings indicated that the US applied for three minutes per treated area improved the organization of the collagen fibers in the tendon repair of rats

To explore the potential mechanisms of tendon degeneration, we investigated the role of c-Jun N-terminal Kinase (JNK) activation and the regulation of matrix metalloproteinase 1 (MMP1) in tendon matrix degradation under oxidative stress. JNK and MMP1 activity in samples from normal and ruptured human supraspinatus tendons were evaluated by immunohistochemistry. Real-time quantitative PCR was utilized to evaluate MMP1 mRNA expression and western blotting for MMP1 and JNK protein detection. JNK activation and increased MMP1 activity were found in the torn human supraspinatus tendon tissue, as well as in human tendon cells under in vitro oxidative stress. Inhibition of JNK prevented MMP1 over-expression in oxidative stressed human tendon cells. Results from the current study indicated that stress activated JNK plays an important role in tendon matrix degradation, possibly through upregulating of MMP1.

<p>The formation and maintenance of tissues in multicellular animals are crucially dependent on cellular interactions with the extracellular matrix (ECM). Two different studies on such interactions are presented herein.</p><p>Studies on expression of laminins in normal and dystrophic skeletal muscle, clarified a much debated issue regarding discrepancies seen for laminin α1-chain expression between human and mouse tissues. Lack of laminin α1-chain expression was verified in both mouse and human skeletal muscle. Furthermore, the earlier discrepancies seen for laminin α1-chain expression was explained by showing that an antibody-reagent, commonly used in human studies, recognised the laminin α5-chain rather than the laminin α1-chain</p><p>The integrin α11-chain (forming α11β1 integrin) is the latest addition to the integrin receptor family, and belongs to the I domain-containing group of integrin α-chains. Previous studies had shown that α11β1 is a collagen receptor. In the present study, the <i>in vitro</i> and <i>in vivo</i> functions of the α11-chain were further characterised. Distribution studies on embryonic human and mouse tissues showed that the α11-chain was expressed on mesenchymal cells in the developing tendon, perichondrium, intervertebral disc, and cornea. The interactions of α11β1 integrin with collagen type I and IV were studied <i>in vitro</i>. The α11β1 bound to these collagens in a manner similar to integrin α2β1 (with collagen type I being the preferred ligand for α11β1). Furthermore, α11β1 was shown to mediate migration on collagen type I coated surfaces, and to mediate contraction of collagen type I gels. The <i>in vivo</i> functions of the α11-chain were investigated by the generation of integrin α11-chain null-mice, using gene targeted disruption of the itga11 in embryonic stem cells. Two independent lines of mice lacking α11 protein were generated. Phenotypic analysis of these mice indicated a role for α11β1 in the formation of the musculoskeletal system.</p>

The formation and maintenance of tissues in multicellular animals are crucially dependent on cellular interactions with the extracellular matrix (ECM). Two different studies on such interactions are presented herein. Studies on expression of laminins in normal and dystrophic skeletal muscle, clarified a much debated issue regarding discrepancies seen for laminin α1-chain expression between human and mouse tissues. Lack of laminin α1-chain expression was verified in both mouse and human skeletal muscle. Furthermore, the earlier discrepancies seen for laminin α1-chain expression was explained by showing that an antibody-reagent, commonly used in human studies, recognised the laminin α5-chain rather than the laminin α1-chain The integrin α11-chain (forming α11β1 integrin) is the latest addition to the integrin receptor family, and belongs to the I domain-containing group of integrin α-chains. Previous studies had shown that α11β1 is a collagen receptor. In the present study, the in vitro and in vivo functions of the α11-chain were further characterised. Distribution studies on embryonic human and mouse tissues showed that the α11-chain was expressed on mesenchymal cells in the developing tendon, perichondrium, intervertebral disc, and cornea. The interactions of α11β1 integrin with collagen type I and IV were studied in vitro. The α11β1 bound to these collagens in a manner similar to integrin α2β1 (with collagen type I being the preferred ligand for α11β1). Furthermore, α11β1 was shown to mediate migration on collagen type I coated surfaces, and to mediate contraction of collagen type I gels. The in vivo functions of the α11-chain were investigated by the generation of integrin α11-chain null-mice, using gene targeted disruption of the itga11 in embryonic stem cells. Two independent lines of mice lacking α11 protein were generated. Phenotypic analysis of these mice indicated a role for α11β1 in the formation of the musculoskeletal system.

Muscle spindles are complex sensory organs that have been strongly implicated in the control and perception of movements. Human muscle spindles in relaxed muscles behave as stretch receptors, responding to the length and velocity of their parent muscles. However, it has been unclear how they discharge during active movements since their discharges are also affected by fusimotor activity and extrafusal contractions. The vast majority of neurophysiological recordings of muscle afferents have been obtained under passive conditions, or active but behaviourally restricted conditions. These restrictions prevent predictions of human muscle afferent activity during purposeful multi-joint movements, naturally occurring during tasks such as hand shaping, grasping or key-pressing. An experimental protocol was therefore developed which allowed recordings of muscle receptor afferent activity using microneurography during unrestrained wrist and digit movements. Along with single afferent discharges, recordings were obtained of electromyographic activity of major forearm muscles and the kinematics of the wrist and digits. This approach allowed investigations of the factors shaping afferent discharge during everyday manual tasks, i.e., block-grasping and pressing sequences of keys, and during active sinusoidal joint movements. The afferents’ ability to encode information concerning the state of the muscle and joint kinematics during these tasks was also assessed. The responses of spindle afferents from load-bearing muscles were approximatelly 90 degrees more phase-advanced than expected on the length of their parent muscles. That is, the discharges of primary muscle spindle afferents were significantly affected by both velocity and acceleration, the discharges of secondary afferents by velocity, and neither afferent type was particularly affected by static muscle length. Accordingly, these afferents failed to encode length, encoded velocity well and acceleration poorly. The representation of muscle length and velocity was, however, significantly improved when the discharge activity of Golgi tendon afferents was taken into consideration along with muscle spindle activity. The discharge of primary afferents during both key-pressing and block-grasping was best correlated to the muscle velocities observed ~100-160 ms in the future. This predictive ability went beyond what could be expected from the spindles’ simultaneous sensitivity to velocity and acceleration, and could thus only be explained by implicating the fusimotor drive. In addition, evidence is presented that the fusimotor control of spindles was contingent on entire movement sequences during the key-pressing task. It is proposed that the phase relationship between the discharge rate of spindle afferents and the length of their parent muscles is load dependent. Moreover, muscle spindles seem to act as forward sensory models of their parent muscle, which makes sensorial feedback control possible despite neural delays.