The telocytes relationship with satellite cells: Extracellular vesicles mediate the myotendinous junction remodeling.

The peripheral nerve injury (PNI) affects the morphology of the whole locomotor apparatus, which can reach the myotendinous junction (MTJ) interface. In the injury condition, the skeletal muscle satellite cells (SC) are triggered, activated, and proliferated to repair their structure, and in the MTJ, the telocytes (TC) are associated to support the interface with the need for remodeling; in that way, these cells can be associated with SC. The study aimed to describe the SC and TC relationship after PNI at the MTJ. Sixteen adult Wistar rats were divided into Control Group (C, n = 8) and PNI Group (PNI, n = 8), PNI was performed by the constriction of the sciatic nerve. The samples were processed for transmission electron microscopy and immunostaining analysis. In the C group was evidenced the arrangement of sarcoplasmic evaginations and invaginations, the support collagen layer with a TC inside it, and an SC through vesicles internally and externally to then. In the PNI group were observed the disarrangement of invaginations and evaginations and sarcomeres degradation at MTJ, as the disposition of telopodes adjacent and in contact to the SC with extracellular vesicles and exosomes in a characterized paracrine activity. These findings can determine a link between the TCs and the SCs at the MTJ remodeling. RESEARCH HIGHLIGHTS: Peripheral nerve injury promotes the myotendinous junction (MTJ) remodeling. The telocytes (TC) and the satellite cells (SC) are present at the myotendinous interface. TC mediated the SC activity at MTJ.

Myotendinous Junction: Exercise Protocols Can Positively Influence Their Development in Rats.

The myotendinous junction (MTJ) is an interface that different stimuli alter their morphology. One of the main stimuli to promote alterations in the MTJ morphology is physical exercise. The present study aimed to investigate the morphology and molecular MTJ adaptations of biceps brachii muscle in adult Wistar rats submitted to different ladder-based protocols. Forty Wistar rats (90 days old) were divided into four groups: Sedentary (S), Climbing (C), Overload Climbing (OC), Climbing, and Overload Climbing (COC). The results of light microscopy demonstrated the cell and collagen tissue reorganization in the experimental groups. The sarcomeres lengths of different regions showed a particular development according to the specific protocols. The sarcoplasmic invaginations and evaginations demonstrated positive increases that promoted the myotendinous interface development. In the extracellular matrix, the structures presented an increase principally in the COC group. Finally, the immunofluorescence analysis showed the telocytes disposition adjacent to the MTJ region in all experimental groups, revealing their network organization. Thus, we concluded that the different protocols contributed to the morphological adaptations with beneficial effects in distinct ways of tissue and cellular development and can be used as a model for MTJ remodeling to future proteomic and genetic analysis.

Miositis del subescapular. Una evolución infrecuente en la tendinopatía calcificada. Estudio de un caso / Subscapularis myositis: An uncommon complication in calcific tendinopathy. A case study

RESUMEN La tendinopatía calcificada del hombro se caracteriza por el depósito de cristales de hidroxiapatita en uno o varios tendones del hombro. Dentro de los procesos que ocurren en esta entidad está la fase de reabsorción, en la que los depósitos podrían migrar hacia estructuras adyacentes. Una muy rara complicación es la migración hacia la unión miotendinosa del tendón correspondiente, la cual provoca una importante reacción inflamatoria muscular que puede objetivarse en pruebas complementarias específicas. Presentamos un caso clínico de una tendinopatía calcificante del subescapular, con pos terior migración hacia la unión miotendinosa causando una miositis del mismo.

ABSTRACT Calcific tendinopathy of the shoulder is characterised by the deposit of hydroxy apatite crys tals in one or more tendons of the shoulder. Within the processes that occur within this disorder, there is the resorption phase, in which the deposits could migrate towards adjacent structures. A very rare complication is the migration towards the myotendinous junction of the corresponding tendon, which causes a significant muscular inflammatory reaction that can be seen in specific complementary tests. A clinical case is presented of a subscapular calcific tendinopathy, with subsequent migra tion to the myotendinous junction, causing myositis of the same.

Myotendinous Junction Components of Different Skeletal Muscles Present Morphological Changes in Obese Rats.

Obesity is characterized by excess adipose tissue and chronic inflammation and promotes extensive changes that can compromise skeletal muscles' structural and functional integrity. Obesity can seriously impact the force transmission region between the muscle and the tendon, the myotendinous junction (MTJ). The present study aimed to investigate the plasticity of muscle fibers and MTJ regions in high-fat diet-induced obesity in rat tibialis anterior (TA) and soleus (SO) muscles. Wistar rats were divided into control and obese groups (induced by a high-fat diet). The samples of TA and SO muscles were prepared for histochemical and ultrastructural analysis (sarcomeres and MTJ projection). In the muscle fiber, similar adaptations were observed between the muscles of the smaller fiber (types I and IIa) in the obesity results. The MTJ region demonstrated different adaptations between the analyzed muscles. The TA­MTJ region has shorter ultrastructures, while in the SO­MTJ region, the ultrastructures were larger. We conclude that obesity induced by a high-fat diet promotes similar adaptation in the muscle fibers; however, in the MTJ region, the sarcoplasmatic projections and adjacent sarcomere demonstrate different adaptations according to distinct muscle phenotypes.

Effects of high loading by eccentric triceps surae training on Achilles tendon properties in humans.

PURPOSE: To document the magnitude and time course of human Achilles tendon adaptations (i.e. changes in tendon morphological and mechanical properties) during a 12-week high-load plantar flexion training program. METHODS: Ultrasound was used to determine Achilles tendon cross-sectional area (CSA), length and elongation as a function of plantar flexion torque during voluntary plantar flexion. Tendon force-elongation and stress-strain relationships were determined before the start of training (pre-training) and after 4 (post-4), 8 (post-8) and 12 (post-12) training weeks. RESULTS: At the end of the training program, maximum isometric force had increased by 49% and tendon CSA by 17%, but tendon length, maximal tendon elongation and maximal strain were unchanged. Hence, tendon stiffness had increased by 82%, and so had Young's modulus, by 86%. Significant changes were first detected at post-4 in stiffness (51% increase) and Young's modulus (87% increase), and at post-8 in CSA (15% increase). CONCLUSIONS: Achilles tendon material properties already improved after 4 weeks of high-load training: stiffness increased while CSA remained unchanged. Tendon hypertrophy (increased CSA) was observed after 8 training weeks and contributed to a further increase in Achilles tendon stiffness, but tendon stiffness increases were mostly caused by adaptations in tissue properties.

Myotendinous junction plasticity in aged ovariectomized rats submitted to aquatic training.

The study aims to describe the tissue plasticity of MTJ through the morphological analysis of MTJ soleus in ovariectomized aged female Wistar rats submitted to aquatic training. Forty aged Wistar rats, 1 year and 2 months of age, were divided into four groups: sedentary (S), trained (T), ovariectomized (O), and trained/ovariectomized (OT). Employing the transmission electron microscopy, the ultrastructural and morphometric elements were revealed. In the S group, changes in morphological characteristics as a consequence of the aging process were seen, demonstrated by the conical shape of the muscle cell extremity, a large area with collagen deposit, and misalignment of sarcomeres in series. The T group presented ample adjustments when revealed the organization of MTJ, through the increase of the contact area and greater lengths of sarcoplasmatic invaginations and evaginations. The O group revealed extensive tissue disorganization with muscle atrophy, reduction of MTJ contact area, and consequently, changes in sarcoplasmatic invaginations and evaginations. The OT group demonstrated extensive remodeling with restructuring MTJ through the increase of tissue contact area, extensive organization, parallel arrangement, and increased length of sarcoplasmatic invaginations and evaginations. The distal sarcomeres presented higher lengths compared to the proximal sarcomeres in both the groups. We conclude that aquatic training was effective in the organization and structural remodeling of the myotendinous interface of ovariectomized aged rats. There was a greater area of contact, and consequently, greater resistance in the myotendinous interface promoting a lower predisposition to injuries.

Mechanical Control of Myotendinous Junction Formation and Tendon Differentiation during Development.

The development of the musculoskeletal system is a great model to study the interplay between chemical and mechanical inter-tissue signaling in cell adhesion, tissue morphogenesis and differentiation. In both vertebrates and invertebrates (e.g., Drosophila melanogaster) the formation of muscle-tendon interaction generates mechanical forces which are required for myotendinous junction maturation and tissue differentiation. In addition, these forces must be withstood by muscles and tendons in order to prevent detachment from each other, deformation or even losing their integrity. Extracellular matrix remodeling at the myotendinous junction is key to resist mechanical load generated by muscle contraction. Recent evidences in vertebrates indicate that mechanical forces generated during junction formation regulate chemical signaling leading to extracellular matrix remodeling, however, the mechanotransduction mechanisms associated to this response remains elusive. In addition to extracellular matrix remodeling, the ability of Drosophila tendon-cells to bear mechanical load depends on rearrangement of tendon cell cytoskeleton, thus studying the molecular mechanisms involved in this process is critical to understand the contribution of mechanical forces to the development of the musculoskeletal system. Here, we review recent findings regarding the role of chemical and mechanical signaling in myotendinous junction formation and tendon differentiation, and discuss molecular mechanisms of mechanotransduction that may allow tendon cells to withstand mechanical load during development of the musculoskeletal system.

Establishment of the Muscle-Tendon Junction During Thorax Morphogenesis in Drosophila Requires the Rho-Kinase.

The assembly of the musculoskeletal system in Drosophila relies on the integration of chemical and mechanical signaling between the developing muscles with ectodermal cells specialized as "tendon cells." Mechanical tension generated at the junction of flight muscles and tendon cells of the notum epithelium is required for muscle morphogenesis, and is balanced by the epithelium in order to not deform. We report that Drosophila Rho kinase (DRok) is necessary in tendon cells to assemble stable myotendinous junctions (MTJ), which are required for muscle morphogenesis and survival. In addition, DRok is required in tendon cells to maintain epithelial shape and cell orientation in the notum, independently of chascon (chas). Loss of DRok function in tendon cells results in mis-orientation of tendon cell extensions and abnormal accumulation of Thrombospondin and ßPS-integrin, which may cause abnormal myotendinous junction formation and muscle morphogenesis. This role does not depend exclusively on nonmuscular Myosin-II activation (Myo-II), indicating that other DRok targets are key in this process. We propose that DRok function in tendon cells is key to promote the establishment of MTJ attachment and to balance mechanical tension generated at the MTJ by muscle compaction.

MRI findings of rotator cuff myotendinous junction injury.

OBJECTIVE: The purpose of this article is to describe the MRI features of rotator cuff myotendinous junction injuries. MATERIALS AND METHODS: We retrospectively identified MRI cases with myotendinous junction injury of the rotator cuff muscles and reviewed clinical, imaging, and surgical records. MR images were reviewed independently by two musculoskeletal radiologists to grade myotendinous junction injuries (strain, partial tear, or complete tear) and to assess for concurrent tendon tears (partial or full thickness) and bone changes (fracture or contusion). RESULTS: The final study group comprised 16 subjects. The mean age was 38 years, with a majority of men (56%). The left shoulder was affected in 56% of subjects, with the dominant upper limb affected in 50%. The mean time between symptoms and MRI was 19 days. Subjects reported heavy lifting (19%), landing on the arm after a fall (19%), or prior shoulder therapeutic injection (25%). Myotendinous junction injuries affected the infraspinatus muscle (50%), followed by the supraspinatus (31%), subscapularis (25%), and teres minor (19%) muscles. About one fifth of subjects presented with more than one muscle affected, and 94% did not present with tears of the corresponding tendons. Most myotendinous junction injuries were strains (80%), followed by partial tears (20%). No complete tears were identified. There was no correlation between myotendinous junction injury and the presence of bone changes or the presence of tendon tears (p > 0.05). CONCLUSION: Rotator cuff myotendinous junction injuries affect mostly the infra-spinatus and supraspinatus muscles, usually in a strain pattern and without tear of the corresponding tendon attachment.