RESUMO
Entheses transmit force from tendons and ligaments to the skeleton. Regional organization of enthesis extracellular matrix (ECM) generates differences in stiffness required for force transmission. Two key transcription factors co-expressed in entheseal tenocytes, scleraxis (Scx) and Sox9, directly control production of enthesis ECM components. Formation of embryonic craniofacial entheses in zebrafish coincides with onset of jaw movements, possibly in response to the force of muscle contraction. We show dynamic changes in scxa and sox9a mRNA levels in subsets of entheseal tenocytes that correlate with their roles in force transmission. We also show that transcription of a direct target of Scxa, Col1a, in enthesis ECM is regulated by the ratio of scxa to sox9a expression. Eliminating muscle contraction by paralyzing embryos during early stages of musculoskeletal differentiation alters relative levels of scxa and sox9a in entheses, primarily owing to increased sox9a expression. Force-dependent TGF-ß (TGFß) signaling is required to maintain this balance of scxa and sox9a expression. Thus, force from muscle contraction helps establish a balance of transcription factor expression that controls specialized ECM organization at the tendon enthesis and its ability to transmit force.
Assuntos
Tendões , Peixe-Zebra , Animais , Peixe-Zebra/genética , Tendões/metabolismo , Osso e Ossos , Transdução de Sinais , LigamentosRESUMO
Movement of the vertebrate body is supported by the connection of muscle, tendon and bone. Each skeletal muscle in the vertebrate body has a unique shape and attachment site; however, the mechanism that ensures reproducible muscle patterning is incompletely understood. In this study, we conducted targeted cell ablation using scleraxis (Scx)-Cre to examine the role of Scx-lineage cells in muscle morphogenesis and attachment in mouse embryos. We found that muscle bundle shapes and attachment sites were significantly altered in embryos with Scx-lineage cell ablation. Muscles in the forelimb showed impaired bundle separation and limb girdle muscles distally dislocated from their insertion sites. Scx-lineage cells were required for post-fusion myofiber morphology, but not for the initial segregation of myoblasts in the limb bud. Furthermore, muscles could change their attachment site, even after formation of the insertion. Lineage tracing suggested that the muscle patterning defect was primarily attributed to the reduction of tendon/ligament cells. Our study demonstrates an essential role of Scx-lineage cells in the reproducibility of skeletal muscle attachment, in turn revealing a previously unappreciated tissue-tissue interaction in musculoskeletal morphogenesis.
Assuntos
Osso e Ossos , Tendões , Camundongos , Animais , Reprodutibilidade dos Testes , Membro Anterior , Músculo Esquelético , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genéticaRESUMO
Tendinopathy is a disorder of musculoskeletal system that primarily affects athletes and the elderly. Current treatment options are generally comprised of various exercise and loading programs, therapeutic modalities, and surgical interventions and are limited to pain management. This study is to understand the role of TRIM54 (tripartite motif containing 54) in tendonitis through in vitro modeling with tendon-derived stem cells (TDSCs) and in vivo using rat tendon injury model. Initially, we observed that TRIM54 overexpression in TDSCs model increased stemness and decreased apoptosis. Additionally, it rescued cells from tumor necrosis factor α-induced inflammation, migration, and tenogenic differentiation. Further, through immunoprecipitation studies, we identified that TRIM54 regulates inflammation in TDSCs by binding to and ubiquitinating YOD1. Further, overexpression of TRIM54 improved the histopathological score of tendon injury as well as the failure load, stiffness, and young modulus in vivo. These results indicated that TRIM54 played a critical role in reducing the effects of tendon injury. Consequently, these results shed light on potential therapeutic alternatives for treating tendinopathy.
Assuntos
Endopeptidases , Proteínas Musculares , Tendinopatia , Tioléster Hidrolases , Idoso , Animais , Humanos , Ratos , Apoptose , Diferenciação Celular/fisiologia , Endopeptidases/metabolismo , Células-Tronco , Tendinopatia/metabolismo , Traumatismos dos Tendões/terapia , Traumatismos dos Tendões/metabolismo , Tendões/metabolismo , Tioléster Hidrolases/metabolismo , Proteínas Musculares/metabolismoRESUMO
The myotendinous junction (MTJ) is a specialized domain of the multinucleated myofibre that is faced with the challenge of maintaining robust cell-matrix contact with the tendon under high mechanical stress and strain. Here, we profiled 24,124 nuclei in semitendinosus muscle-tendon samples from three healthy males by using single-nucleus RNA sequencing (snRNA-seq), alongside spatial transcriptomics, to gain insight into the genes characterizing this specialization in humans. We identified a cluster of MTJ myonuclei represented by 47 enriched transcripts, of which the presence of ABI3BP, ABLIM1, ADAMTSL1, BICD1, CPM, FHOD3, FRAS1 and FREM2 was confirmed at the MTJ at the protein level in immunofluorescence assays. Four distinct subclusters of MTJ myonuclei were apparent, comprising two COL22A1-expressing subclusters and two subclusters lacking COL22A1 expression but with differing fibre type profiles characterized by expression of either MYH7 or MYH1 and/or MYH2. Our findings reveal distinct myonuclei profiles of the human MTJ, which represents a weak link in the musculoskeletal system that is selectively affected in pathological conditions ranging from muscle strains to muscular dystrophies.
Assuntos
Junção Miotendínea , Tendões , Masculino , Humanos , Tendões/fisiologia , Núcleo Celular/metabolismo , Músculo Esquelético/metabolismo , Proteínas dos Microfilamentos/metabolismo , Proteínas com Domínio LIM/metabolismo , Proteínas do Citoesqueleto/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Forminas/metabolismoRESUMO
Hyaluronan (HA) plays well-recognized mechanical and biological roles in articular cartilage and synovial fluid, where it contributes to tissue structure and lubrication. An understanding of how HA contributes to the structure of other musculoskeletal tissues, including muscle, bone, tendon, and intervertebral discs, is growing. In addition, the use of HA-based therapies to restore damaged tissue is becoming more prevalent. Nevertheless, the relationship between biomechanical stimuli and HA synthesis, degradation, and signaling in musculoskeletal tissues remains understudied, limiting the utility of HA in regenerative medicine. In this review, we discuss the various roles and significance of endogenous HA in musculoskeletal tissues. We use what is known and unknown to motivate new lines of inquiry into HA biology within musculoskeletal tissues and in the mechanobiology governing HA metabolism by suggesting questions that remain regarding the relationship and interaction between biological and mechanical roles of HA in musculoskeletal health and disease.
Assuntos
Ácido Hialurônico , Tendões , Ácido Hialurônico/química , Humanos , Animais , Fenômenos Biomecânicos , Tendões/fisiologia , Tendões/metabolismo , Cartilagem Articular/fisiologia , Cartilagem Articular/metabolismo , Transdução de Sinais , Osso e Ossos/metabolismo , Osso e Ossos/fisiologia , Líquido Sinovial/metabolismo , Líquido Sinovial/fisiologia , Músculo Esquelético/fisiologia , Músculo Esquelético/metabolismo , Sistema Musculoesquelético/metabolismo , Medicina Regenerativa/métodosRESUMO
The development of musculoskeletal tissues such as tendon, enthesis, and bone relies on proliferation and differentiation of mesenchymal progenitor cells. Gli1+ cells have been described as putative stem cells in several tissues and are presumed to play critical roles in tissue formation and maintenance. For example, the enthesis, a fibrocartilage tissue that connects tendon to bone, is mineralized postnatally by a pool of Gli1+ progenitor cells. These cells are regulated by hedgehog signaling, but it is unclear if TGFß signaling, necessary for tenogenesis, also plays a role in their behavior. To examine the role of TGFß signaling in Gli1+ cell function, the receptor for TGFß, TbR2, was deleted in Gli1-lineage cells in mice at P5. Decreased TGFß signaling in these cells led to defects in tendon enthesis formation by P56, including defective bone morphometry underlying the enthesis and decreased mechanical properties. Immunohistochemical staining of these Gli1+ cells showed that loss of TGFß signaling reduced proliferation and increased apoptosis. In vitro experiments using Gli1+ cells isolated from mouse tail tendons demonstrated that TGFß controls cell proliferation and differentiation through canonical and non-canonical pathways and that TGFß directly controls the tendon transcription factor scleraxis by binding to its distant enhancer. These results have implications in the development of treatments for tendon and enthesis pathologies.
Assuntos
Proteínas Hedgehog , Fator de Crescimento Transformador beta , Animais , Camundongos , Proteínas Hedgehog/genética , Proteína GLI1 em Dedos de Zinco/genética , Tendões , Transdução de SinaisRESUMO
The molecular and cellular basis of health in human tendons remains poorly understood. Among human tendons, hamstring tendon has markedly low pathology and can provide a prototypic healthy tendon reference. The aim of this study was to determine the transcriptomes and location of all cell types in healthy hamstring tendon. Using single nucleus RNA sequencing, we profiled the transcriptomes of 10 533 nuclei from four healthy donors and identified 12 distinct cell types. We confirmed the presence of two fibroblast cell types, endothelial cells, mural cells, and immune cells, and identified cell types previously unreported in tendons, including different skeletal muscle cell types, satellite cells, adipocytes, and undefined nervous system cells. The location of these cell types within tendon was defined using spatial transcriptomics and imaging, and potential transcriptional networks and cell-cell interactions were analyzed. We demonstrate that fibroblasts have the highest number of potential cell-cell interactions in our dataset, are present throughout the tendon, and play an important role in the production and organization of extracellular matrix, thus confirming their role as key regulators of hamstring tendon homeostasis. Overall, our findings underscore the complexity of the cellular networks that underpin healthy human tendon function and the central role of fibroblasts as key regulators of hamstring tendon tissue homeostasis.
Assuntos
Perfilação da Expressão Gênica , Tendões dos Músculos Isquiotibiais , Transcriptoma , Humanos , Masculino , Adulto , Tendões dos Músculos Isquiotibiais/metabolismo , Fibroblastos/metabolismo , Feminino , Núcleo Celular/metabolismo , Núcleo Celular/genética , Matriz Extracelular/metabolismo , Tendões/metabolismoRESUMO
Computational models of musculoskeletal systems are essential tools for understanding how muscles, tendons, bones, and actuation signals generate motion. In particular, the OpenSim family of models has facilitated a wide range of studies on diverse human motions, clinical studies of gait, and even non-human locomotion. However, biological structures with many joints, such as fingers, necks, tails, and spines, have been a longstanding challenge to the OpenSim modeling community, especially because these structures comprise numerous bones and are frequently actuated by extrinsic muscles that span multiple joints-often more than three-and act through a complex network of branching tendons. Existing model building software, typically optimized for limb structures, makes it difficult to build OpenSim models that accurately reflect these intricacies. Here, we introduce ArborSim, customized software that efficiently creates musculoskeletal models of highly jointed structures and can build branched muscle-tendon architectures. We used ArborSim to construct toy models of articulated structures to determine which morphological features make a structure most sensitive to branching. By comparing the joint kinematics of models constructed with branched and parallel muscle-tendon units, we found that among various parameters-the number of tendon branches, the number of joints between branches, and the ratio of muscle fiber length to muscle tendon unit length-the number of tendon branches and the number of joints between branches are most sensitive to branching modeling method. Notably, the differences between these models showed no predictable pattern with increased complexity. As the proportion of muscle increased, the kinematic differences between branched and parallel models units also increased. Our findings suggest that stress and strain interactions between distal tendon branches and proximal tendon and muscle greatly affect the overall kinematics of a musculoskeletal system. By incorporating complex muscle-tendon branching into OpenSim models using ArborSim, we can gain deeper insight into the interactions between the axial and appendicular skeleton, model the evolution and function of diverse animal tails, and understand the mechanics of more complex motions and tasks.
Assuntos
Articulações , Músculo Esquelético , Software , Tendões , Tendões/fisiologia , Tendões/anatomia & histologia , Humanos , Fenômenos Biomecânicos , Articulações/fisiologia , Articulações/anatomia & histologia , Músculo Esquelético/fisiologia , Músculo Esquelético/anatomia & histologia , Modelos Biológicos , Biologia Computacional , Simulação por Computador , AnimaisRESUMO
Heterotopic ossification (HO) occurs as a common complication after injury, while its risk factor and mechanism remain unclear, which restricts the development of pharmacological treatment. Clinical research suggests that diabetes mellitus (DM) patients are prone to developing HO in the tendon, but solid evidence and mechanical research are still needed. Here, we combined the clinical samples and the DM mice model to identify that disordered glycolipid metabolism aggravates the senescence of tendon-derived stem cells (TSCs) and promotes osteogenic differentiation. Then, combining the RNA-seq results of the aging tendon, we detected the abnormally activated autocrine CXCL13-CXCR5 axis in TSCs cultured in a high fat, high glucose (HFHG) environment and also in the aged tendon. Genetic inhibition of CXCL13 successfully alleviated HO formation in DM mice, providing a potential therapeutic target for suppressing HO formation in DM patients after trauma or surgery.
Assuntos
Quimiocina CXCL13 , Glicolipídeos , Ossificação Heterotópica , Osteogênese , Receptores CXCR5 , Animais , Ossificação Heterotópica/metabolismo , Ossificação Heterotópica/patologia , Ossificação Heterotópica/genética , Camundongos , Humanos , Quimiocina CXCL13/metabolismo , Quimiocina CXCL13/genética , Glicolipídeos/metabolismo , Receptores CXCR5/metabolismo , Receptores CXCR5/genética , Células-Tronco/metabolismo , Tendões/metabolismo , Tendões/patologia , Masculino , Camundongos Endogâmicos C57BL , Diferenciação Celular , Senescência Celular , Transdução de Sinais , Células Cultivadas , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologiaRESUMO
The imbalance between endogenous and exogenous healing is the fundamental reason for the poor tendon healing. In this study, a Janus patch was developed to promote endogenous healing and inhibit exogenous healing, leading to improved tendon repair. The upper layer of the patch is a poly(dl-lactide-co-glycolide)/polycaprolactone (PLGA/PCL) nanomembrane (PMCP-NM) modified with poly(2-methylacryloxyethyl phosphocholine) (PMPC), which created a lubricated and antifouling surface, preventing cell invasion and mechanical activation. The lower layer is a PLGA/PCL fiber membrane loaded with fibrin (Fb) (Fb-NM), serving as a temporary chemotactic scaffold to regulate the regenerative microenvironment. In vitro, the Janus patch effectively reduced 92.41% cell adhesion and 79.89% motion friction. In vivo, the patch inhibited tendon adhesion through the TGF-ß/Smad signaling pathway and promoted tendon maturation. This Janus patch is expected to provide a practical basis and theoretical guidance for high-quality soft tissue repair.
Assuntos
Tendões , Cicatrização , Tendões/fisiologia , Adesão CelularRESUMO
Although the functions of the peripheral nervous system in whole body homeostasis and sensation have been understood for many years, recent investigation has uncovered new roles for innervation in the musculoskeletal system. This review centers on advances regarding the function of nerves in the development and repair of two connected tissues: tendon and bone. Innervation in healthy tendons is generally confined to the tendon sheaths, and tendon-bone attachment units are typically aneural. In contrast to tendon, bone is an innervated and vascularized structure. Historically, the function of abundant peripheral nerves in bone has been limited to pain and some non-painful sensory perception in disease and injury. Indeed, much of our understanding of peripheral nerves in tendons, bones, and entheses is limited to the source and type of innervation in healthy and injured tissues. However, more recent studies have made important observations regarding the appearance, type, and innervation patterns of nerves during embryonic and postnatal development and in response to injury, which suggest a more expansive role for peripheral nerves in the formation of musculoskeletal tissues. Indeed, tendons and bones develop in a close spatiotemporal relationship in the embryonic mesoderm. Models of limb denervation have shed light on the importance of sensory innervation in bone and to a lesser extent, tendon development, and more recent work has unraveled key nerve signaling pathways. Furthermore, loss of sensory innervation also impairs healing of bone fractures and may contribute to chronic tendinopathy. However, more study is required to translate our knowledge of peripheral nerves to therapeutic strategies to combat bone and tendon diseases.
Assuntos
Osso e Ossos , Tendões , Homeostase , Nervos Periféricos , Tendões/inervaçãoRESUMO
Tendons are cable-like connective tissues that transfer both active and passive forces generated by skeletal muscle to bone. In the mature skeleton, the tendon-bone enthesis is an interfacial zone of transitional tissue located between two mechanically dissimilar tissues: compliant, fibrous tendon to rigid, dense mineralized bone. In this review, we focus on emerging areas in enthesis development related to its structure, function, and mechanobiology, as well as highlight established and emerging signaling pathways and physiological processes that influence the formation and adaptation of this important transitional tissue.
Assuntos
Osso e Ossos , Tendões , Biofísica , Músculo Esquelético , Transdução de Sinais , Tendões/fisiologiaRESUMO
The pathogenesis of trauma-induced heterotopic ossification (HO) in the tendon remains unclear, posing a challenging hurdle in treatment. Recognizing inflammation as the root cause of HO, anti-inflammatory agents hold promise for its management. Malvidin (MA), possessing anti-inflammatory properties, emerges as a potential agent to impede HO progression. This study aimed to investigate the effect of MA in treating trauma-induced HO and unravel its underlying mechanisms. Herein, the effectiveness of MA in preventing HO formation was assessed through local injection in a rat model. The potential mechanism underlying MA's treatment was investigated in the tendon-resident progenitor cells of tendon-derived stem cells (TDSCs), exploring its pathway in HO formation. The findings demonstrated that MA effectively hindered the osteogenic differentiation of TDSCs by inhibiting the mTORC1 signalling pathway, consequently impeding the progression of trauma-induced HO of Achilles tendon in rats. Specifically, MA facilitated the degradation of Rheb through the K48-linked ubiquitination-proteasome pathway by modulating USP4 and intercepted the interaction between Rheb and the mTORC1 complex, thus inhibiting the mTORC1 signalling pathway. Hence, MA presents itself as a promising candidate for treating trauma-induced HO in the Achilles tendon, acting by targeting Rheb for degradation through the ubiquitin-proteasome pathway.
Assuntos
Ossificação Heterotópica , Complexo de Endopeptidases do Proteassoma , Proteína Enriquecida em Homólogo de Ras do Encéfalo , Transdução de Sinais , Ubiquitina , Animais , Ratos , Complexo de Endopeptidases do Proteassoma/metabolismo , Ossificação Heterotópica/metabolismo , Ossificação Heterotópica/etiologia , Ossificação Heterotópica/patologia , Transdução de Sinais/efeitos dos fármacos , Proteína Enriquecida em Homólogo de Ras do Encéfalo/metabolismo , Ubiquitina/metabolismo , Masculino , Osteogênese/efeitos dos fármacos , Tendões/metabolismo , Tendões/patologia , Ratos Sprague-Dawley , Traumatismos dos Tendões/metabolismo , Traumatismos dos Tendões/patologia , Traumatismos dos Tendões/complicações , Proteólise/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Tendão do Calcâneo/metabolismo , Tendão do Calcâneo/patologia , Tendão do Calcâneo/lesões , Modelos Animais de Doenças , Ubiquitinação , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Células-Tronco/metabolismo , Células-Tronco/efeitos dos fármacosRESUMO
Previous in vitro and in situ studies have reported a shift in optimal muscle fibre length for force generation (L0) towards longer length at decreasing activation levels (also referred to as length-dependent activation), yet the relevance for in vivo human muscle contractions with a variable activation pattern remains largely unclear. By a combination of dynamometry, ultrasound and electromyography (EMG), we experimentally obtained muscle force-fascicle length curves of the human soleus at 100%, 60% and 30% EMGmax levels from 15 participants aiming to investigate activation-dependent shifts in L0 in vivo. The results showed a significant increase in L0 of 6.5 ± 6.0% from 100% to 60% EMGmax and of 9.1 ± 7.2% from 100% to 30% EMGmax (both P < 0.001), respectively, providing evidence of a moderate in vivo activation dependence of the soleus force-length relationship. Based on the experimental results, an approximation model of an activation-dependent force-length relationship was defined for each individual separately and for the collective data of all participants, both with sufficiently high accuracy (R2 of 0.899 ± 0.056 and R2 = 0.858). This individual approximation approach and the general approximation model outcome are freely accessible and may be used to integrate activation-dependent shifts in L0 in experimental and musculoskeletal modelling studies to improve muscle force predictions. KEY POINTS: The phenomenon of the activation-dependent shift in optimal muscle fibre length for force generation (length-dependent activation) is poorly understood for human muscle in vivo dynamic contractions. We experimentally observed a moderate shift in optimal fascicle length towards longer length at decreasing electromyographic activity levels for the human soleus muscle in vivo. Based on the experimental results, we developed a freely accessible approximation model that allows the consideration of activation-dependent shifts in optimal length in future experimental and musculoskeletal modelling studies to improve muscle force predictions.
Assuntos
Músculo Esquelético , Tendões , Humanos , Tendões/fisiologia , Fenômenos Biomecânicos , Músculo Esquelético/fisiologia , Contração Muscular/fisiologia , EletromiografiaRESUMO
Residual force depression (rFD) following active muscle shortening is assumed to correlate most strongly with muscle work, but this has not been tested during voluntary contractions in humans. Using dynamometry, we compared steady-state ankle joint torques (N = 16) following tibialis anterior (TA) muscle-tendon unit (MTU) lengthening and shortening to the time-matched torque during submaximal voluntary fixed-end dorsiflexion reference contractions (REF) at a matched MTU length and EMG amplitude. Ultrasound revealed significantly reduced (P < 0.001) TA fascicle shortening amplitudes during MTU lengthening without a preload over small and medium amplitudes, respectively, relative to REF. MTU lengthening with a preload over a large amplitude significantly (P < 0.001) increased fascicle shortening relative to REF, as well as stretch amplitudes relative to MTU lengthening without a preload (P = 0.001). Significant (P = 0.028) steady-state fascicle force enhancement relative to REF was observed following MTU lengthening, and was similar among MTU lengthening-hold conditions (3-5%). MTU shortening with and without a preload over small and large amplitudes significantly (P < 0.001) increased positive fascicle and MTU work relative to REF, but significant (P = 0.006) rFD was observed following MTU shortening with a preload (7-10%) only. rFD was linearly related to positive MTU work [rrm (47) = 0.48, P < 0.001], but not positive fascicle work [rrm (47) = 0.16, P = 0.277]. Our findings indicate that MTU lengthening without substantial fascicle stretch enhances steady-state force output, which might arise from less shortening-induced rFD. Our findings also indicate similar rFD following different amounts of positive fascicle/MTU work, which cautions against using work to predict rFD during submaximal voluntary contractions. KEY POINTS: Accurately predicting muscle force is challenging because active muscle shortening depresses force output. The residual force depression (rFD) that exists following active muscle shortening is commonly assumed to correlate strongly and positively with muscle work. We found that tibialis anterior muscle fascicle work and muscle-tendon unit work did not accurately predict rFD during submaximal voluntary dorsiflexion contractions. Fascicle shortening during fixed-end reference contractions also potentially induced rFD of 3-5%, which was similar to the rFD following muscle-tendon unit shortening without a preload. A higher number of active muscle fibres during shortening probably increased rFD, which suggests that motor unit recruitment during shortening might predict rFD.
Assuntos
Depressão , Músculo Esquelético , Humanos , Músculo Esquelético/fisiologia , Tendões/fisiologia , Fibras Musculares Esqueléticas , Articulação do Tornozelo , Contração Muscular/fisiologia , Contração Isométrica/fisiologia , EletromiografiaRESUMO
Local vibration (LV) applied over the muscle tendon constitutes a powerful stimulus to activate the muscle spindle primary (Ia) afferents that project to the spinal level and are conveyed to the cortical level. This study aimed to identify the neuromuscular changes induced by a 30-min LV-inducing illusions of hand extension on the vibrated flexor carpi radialis (FCR) and the antagonist extensor carpi radialis (ECR) muscles. We studied the change of the maximal voluntary isometric contraction (MVIC, experiment 1) for carpal flexion and extension, motor-evoked potentials (MEPs, experiment 2), cervicomedullary motor-evoked potentials (CMEPs, experiment 2), and Hoffmann's reflex (H-reflex, experiment 3) for both muscles at rest. Measurements were performed before (PRE) and at 0, 30, and 60 min after LV protocol. A lasting decrease in strength was only observed for the vibrated muscle. The reduction in CMEPs observed for both muscles seems to support a decrease in alpha motoneurons excitability. In contrast, a slight decrease in MEPs responses was observed only for the vibrated muscle. The MEP/CMEP ratio increase suggested greater cortical excitability after LV for both muscles. In addition, the H-reflex largely decreased for the vibrated and the antagonist muscles. The decrease in the H/CMEP ratio for the vibrated muscle supported both pre- and postsynaptic causes of the decrease in the H-reflex. Finally, LV-inducing illusions of movement reduced alpha motoneurons excitability for both muscles with a concomitant increase in cortical excitability.NEW & NOTEWORTHY Spinal disturbances confound the interpretation of excitability changes in motor areas and compromise the conclusions reached by previous studies using only a corticospinal marker for both vibrated and antagonist muscles. The time course recovery suggests that the H-reflex perturbations for the vibrated muscle do not only depend on changes in alpha motoneurons excitability. Local vibration induces neuromuscular changes in both vibrated and antagonist muscles at the spinal and cortical levels.
Assuntos
Ilusões , Humanos , Eletromiografia/métodos , Ilusões/fisiologia , Vibração , Músculo Esquelético/fisiologia , Tendões/fisiologia , Potencial Evocado Motor/fisiologia , Tratos Piramidais/fisiologia , Estimulação Magnética Transcraniana/métodosRESUMO
Tendons and ligaments are fibrous connective tissues vital to the transmission of force and stabilization of the musculoskeletal system. Arising in precise regions of the embryo, tendons and ligaments share many properties and little is known about the molecular differences that differentiate them. Recent studies have revealed heterogeneity and plasticity within tendon and ligament cells, raising questions regarding the developmental mechanisms regulating tendon and ligament identity. Here, we discuss recent findings that contribute to our understanding of the mechanisms that establish and maintain tendon progenitors and their differentiated progeny in the head, trunk and limb. We also review the extent to which these findings are specific to certain anatomical regions and model organisms, and indicate which findings similarly apply to ligaments. Finally, we address current research regarding the cellular lineages that contribute to tendon and ligament repair, and to what extent their regulation is conserved within tendon and ligament development.
Assuntos
Diferenciação Celular , Ligamentos/embriologia , Desenvolvimento Musculoesquelético , Células-Tronco/metabolismo , Tendões/embriologia , Animais , Humanos , Ligamentos/citologia , Células-Tronco/citologia , Tendões/citologiaRESUMO
The re-tear rate of rotator cuff tears (RCT) after surgical repair is high, especially in aged patients with chronic tears. Senescent tendon stem cells (s-TSCs) generally exist in aged and chronically torn rotator cuff tendons and are closely associated with impaired tendon-to-bone healing results. The present study found a positive feedback cross-talk between s-TSCs and macrophages. The conditioned medium (CM) from s-STCs can promote macrophage polarization mainly toward the M1 phenotype, whose CM reciprocally accelerated further s-TSC senescence. Additional healthy tendon stem-cells derived exosomes (h-TSC-Exos) can break this positive feedback cross-talk by skewing macrophage polarization from the M1 phenotype to the M2 phenotype, attenuating s-TSCs senescence. S-TSC senescence acceleration or attenuation effects induced by M1 or M2 macrophages are associated with the inhibition or activation of the bone morphogenetic protein 4 signaling pathway following RNA sequencing analysis. Using an aged-chronic rotator cuff tear rat model, it is found that h-TSC-Exos can shift the microenvironment in the tendon-to-bone interface from a pro-inflammatory to an anti-inflammatory type at the acute postoperative stage and improve the tendon-to-bone healing results, which are associated with the rejuvenated s-TSCs. Therefore, this study proposed a potential strategy to improve the healing of aged chronic RCT.
Assuntos
Exossomos , Macrófagos , Lesões do Manguito Rotador , Células-Tronco , Tendões , Cicatrização , Exossomos/metabolismo , Animais , Macrófagos/metabolismo , Lesões do Manguito Rotador/patologia , Lesões do Manguito Rotador/metabolismo , Tendões/patologia , Células-Tronco/citologia , Células-Tronco/metabolismo , Ratos , Manguito Rotador/patologia , Masculino , Senescência Celular , Osso e Ossos , Ratos Sprague-Dawley , HumanosRESUMO
PURPOSE: This study aims to assess ultrashort-TE magnetization transfer (UTE-MT) imaging of collagen degradation using an in vitro model of rotator cuff tendinopathy. METHODS: Thirty-six supraspinatus tendon specimens were divided into three groups and treated with 600 U collagenase (Group 1), 150 U collagenase (Group 2), and phosphate buffer saline (Group 3). UTE-MT imaging was performed to assess changes in macromolecular fraction (MMF), macromolecule transverse relaxation time (T2m), water longitudinal relaxation rate constant (R1m), the magnetization exchange rate from the macromolecular to water pool (Rm0 w) and from water to the macromolecular pool (Rm0 m), and magnetization transfer ratio (MTR) at baseline and following digestion and their differences between groups. Biochemical and histological studies were conducted to determine the extent of collagen degradation. Correlation analyses were performed with MMF, T2m, R1m, Rm0 w, Rm0 m, and MTR, respectively. Univariate and multivariate linear regression analyses were performed to evaluate combinations of UTE-MT parameters to predict collagen degradation. RESULTS: MMF, T2m, R1m, Rm0 m, and MTR decreased after digestion. MMF (r = -0.842, p < 0.001), MTR (r = -0.78, p < 0.001), and Rm0 m (r = -0.662, p < 0.001) were strongly negatively correlated with collagen degradation. The linear regression model of differences in MMF and Rm0 m before and after digestion explained 68.9% of collagen degradation variation in the tendon. The model of postdigestion in MMF and T2m and the model of MTR explained 54.2% and 52.3% of collagen degradation variation, respectively. CONCLUSION: This study highlighted the potential of UTE-MT parameters for evaluation of supraspinatus tendinopathy.
Assuntos
Colágeno , Imageamento por Ressonância Magnética , Manguito Rotador , Tendinopatia , Tendinopatia/diagnóstico por imagem , Tendinopatia/metabolismo , Colágeno/metabolismo , Humanos , Manguito Rotador/diagnóstico por imagem , Manguito Rotador/metabolismo , Imageamento por Ressonância Magnética/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Colagenases/metabolismo , Tendões/diagnóstico por imagem , Tendões/metabolismo , Processamento de Imagem Assistida por Computador/métodosRESUMO
The flexor tendon pulleys in the fingers of the hand are fibrous structures of variable size, shape, and thickness that cover the synovial sheath of these tendons. Despite their clinical relevance, their arrangement and configuration in each of the triphalangeal fingers have been little studied and with small sample sizes. 192 triphalangeal fingers belonging to 48 fresh body donors' hands were dissected. Multivariate analysis was carried out. Twenty-five cases (52%) were left hands, and 26 of the 48 hands belonged to female donors (54.2%). The results were analyzed by fingers for each of the 5 annular pulleys, the 3 cruciform pulleys and the gaps between them. In addition, the most and least frequent configurations of the pulleys in each of the fingers were studied, observing that the classic pattern with all the pulleys appeared only in 3 fingers (1.56%), while the most frequent pattern was A1-A2-C1-A3-A4, which was seen in 35 fingers (18.22%). CONCLUSIONS: The flexor pulleys in the triphalangeal fingers of the hand have shown enormous variability in arrangement and shape, and also rarely appear all in the same finger. This peculiar anatomical arrangement can help the different professionals who perform their clinical work in this region.