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Long head of the biceps tendon pathology is a well-described proximal shoulder pain generator. While optimal treatment strategy remains controversial, popular operative management includes biceps tenodesis. However, appropriate restoration of the anatomic length–tension relationship of the biceps with tenodesis remains a challenge. We aim to describe a patient-specific technique utilizing a mini-open subpectoral approach to mark the long head of the biceps myotendinous junction location within the intertubercular groove prior to arthroscopic origin tenotomy. This technique offers the ability to restore anatomic tensioning of the long head of the biceps without relying on variable anatomic relationships, additional portals, tools, or technical challenges. [ABSTRACT FROM AUTHOR]

This review offers a comprehensive discussion of magnetic resonance imaging (MRI) for the assessment of rotator cuff tendon repair and joint-preserving surgical options for patients with irreparable rotator cuff tears. Deciding to proceed with arthroscopic repair of a rotator cuff tendon tear is impacted both by clinical factors and morphological imaging features. Preoperative clinical and imaging features also predict the likelihood of success of a rotator cuff tendon repair and are important to recognize. In patients with irreparable rotator cuff tears and relatively preserved glenohumeral cartilage, various joint-preserving surgical options are available and seen increasingly in clinical practice. The acceptable range of postoperative imaging findings correlating with a functionally intact rotator cuff repaired tendon, and MRI findings that are either suggestive of or definitive for rotator cuff tendon repair failure are discussed in detail, with attention to the Sugaya classification. Ancillary features, such as progressive retraction of the myotendinous junction and the degree of muscle fatty atrophy, can be used as problem-solving tools in cases equivocal for rotator cuff retear. Finally, this review discusses in detail the most common joint-preserving treatment options for patients with irreparable rotator cuff tears, including an in-depth focus on superior capsular reconstruction. [ABSTRACT FROM AUTHOR]

Background: This is a novel rat study using native peptide therapy, focused on reversing quadriceps muscle-to-bone detachment to reattachment and stable gastric pentadecapeptide BPC 157 per-oral therapy for shared muscle healing and function restoration. Methods: Pharmacotherapy recovering various muscle, tendon, ligament, and bone lesions, and severed junctions (i.e., myotendinous junction), per-oral in particular (BPC 157/kg/day 10 µg, 10 ng), provides muscle-to-bone reattachment after quadriceps muscle detachment, both complete (rectus muscle) and partial (vastus muscles). Results: Immediately post-injury, and at 1, 2, 3, 5, 7, 14, 21, 28, 60, and 90 days post-injury, quadriceps muscle-to-bone detachment showed definitive healing failure (impaired walking and permanent knee flexure). Contrarily, macro/microscopic, ultrasonic, magnetic resonance, biomechanical, and functional assessments revealed that BPC 157 therapy recovering effects for all time points were consistent. All parameters of the walking pattern fully improved, and soon after detachment and therapy application, muscle approached the bone, leaving a minimal gap (on ultrasonic assessment), and leg contracture was annihilated. The healing process occurs immediately after detachment from both sides: the muscle and the bone. The reattachment fibers from the ends of the muscle could be traced into the new bone formed at the surface (note, at day 3 post-detachment, increased mesenchymal cells occurred with periosteum reactivation). Consequently, at 3 months, the form was stable, and the balance between the muscle and bone was the following: well-organized bone, newly formed as more cortical bone providing a narrower bone marrow space, and the muscle and mature fibers were oriented parallel to the bone axis and were in close contact with bone. Conclusions: Therefore, to achieve quadriceps muscle-to-bone reattachment, the BPC 157 therapy reversing course acts from the beginning, resolving an otherwise insurmountable deleterious course. [ABSTRACT FROM AUTHOR]

Magnetization transfer (MT) magnetic resonance imaging (MRI) can be used to estimate the fraction of water and macromolecular proton pools in tissues. MT modeling paired with ultrashort echo time acquisition (UTE‐MT modeling) has been proposed to improve the evaluation of the myotendinous junction and fibrosis in muscle tissues, which the latter increases with aging. This study aimed to determine if the UTE‐MT modeling technique is sensitive to age‐related changes in the skeletal muscles of the lower leg. Institutional review board approval was obtained, and all recruited subjects provided written informed consent. The legs of 31 healthy younger (28.1 ± 6.1 years old, BMI = 22.3 ± 3.5) and 20 older (74.7 ± 5.5 years old, BMI = 26.7 ± 5.9) female subjects were imaged using UTE sequences on a 3 T MRI scanner. MT ratio (MTR), macromolecular fraction (MMF), macromolecular T2 (T2‐MM), and water T2 (T2‐W) were calculated using UTE‐MT modeling for the anterior tibialis (ATM), posterior tibialis (PTM), soleus (SM), and combined lateral muscles. Results were compared between groups using the Wilcoxon rank sum test. Three independent observers selected regions of interest (ROIs) and processed UTE‐MRI images separately, and the intraclass correlation coefficient (ICC) was calculated for a reproducibility study. Significantly lower mean MTR and MMF values were present in the older compared with the younger group in all studied lower leg muscles. T2‐MM showed significantly lower values in the older group only for PTM and SM muscles. In contrast, T2‐W showed significantly higher values in the older group. The age‐related differences were more pronounced for MMF (−17 to −19%) and T2‐W (+20 to 47%) measurements in all muscle groups compared with other investigated MR measures. ICCs were higher than 0.93, indicating excellent consistency between the ROI selection and MRI measurements of independent readers. As demonstrated by significant differences between younger and older groups, this research emphasizes the potential of UTE‐MT MRI techniques in evaluating age‐related skeletal muscle changes. [ABSTRACT FROM AUTHOR]

Skeletal muscle formation involves tight interactions between muscle cells and associated connective tissue fibroblasts. Every muscle displays the same type of organisation, they are innervated in the middle and attached at both extremities to tendons. Myonuclei are heterogeneous along myotubes and regionalised according to these middle and tip domains. During development, as soon as myotubes are formed, myonuclei at muscle tips facing developing tendons display their own molecular program. In addition to molecular heterogeneity, a subset of tip myonuclei has a fibroblastic origin different to the classical somitic origin, highlighting a cellular heterogeneity of myonuclei in foetal myotubes. To gain insights on the functional relevance of myonucleus heterogeneity during limb development, we used 2D culture and co-culture systems to dissociate autonomous processes (occurring in 2D-cultures) from 3D-environment of tissue development. We also assessed the role of muscle contraction in myonucleus heterogeneity in paralysed limb muscles. The regionalisation of cellular heterogeneity was not observed in 2D cell culture systems and paralyzed muscles. The molecular signature of MTJ myonuclei was lost in a dish and paralysed muscles indicating a requirement of 3D-enviroment and muscle contraction for MTJ formation. Tip genes that maintain a regionalized expression at myotube tips in cultures are linked to sarcomeres. The behaviour of regionalized markers in cultured myotubes and paralyzed muscles allows us to speculate whether the genes intervene in myogenesis, myotube attachment or MTJ formation. Highlights: • The molecular signature of MTJ myonuclei is lost in cultured myotubes and paralysed muscles • Genes expressed in muscle tips that maintain their regionalised expression in cultured myotubes are linked to sarcomeric proteins • Cellular heterogeneity of myonuclei is observed in cultured myotubes but with no regionalisation • BMP signalling regulates fibroblast nucleus incorporation into cultured myotubes [ABSTRACT FROM AUTHOR]

Volkmann's ischemic contracture is a condition characterized by permanent ischemic damage to muscles and nerves due to vascular insufficiency, resulting in flexion contractures of the affected limb. In contrast, pseudo-Volkmann's contracture presents with similar clinical features but lacks ischemic damage and has the potential for complete recovery. We report a case of a 39-year-old man who developed failure of extension in the middle and ring fingers of the left hand following blunt forearm trauma from a rolling machine. Despite no skin breakage or fracture, his symptoms progressively worsened over 2 months without treatment. Surgical exploration 2 years later revealed severe adhesions of the flexor digitorum profundus muscle at the myotendinous junction to the ulnar periosteum, with immediate recovery after release. This case highlights pseudo-Volkmann's contracture in an adult without fracture, likely due to blunt trauma causing delayed adhesion formation. [ABSTRACT FROM AUTHOR]

The article discusses the use of platelet-poor plasma (PPP) in treating a quadriceps muscle tear in a Division I football athlete. The athlete presented with acute thigh pain, and a grade 3 tear was confirmed through diagnostic ultrasound. Two consecutive PPP injections were administered, leading to complete resolution of pain and full healing of the injury within 18 days. The case demonstrates a rapid return to high-level activity, suggesting PPP as a promising treatment for muscle injuries, although further studies are needed for confirmation. [Extracted from the article]

Purpose: The rectus femoris forms the anterior portion of the quadriceps muscle. It has a proximal tendinous complex, which is constituted by a direct tendon, an indirect tendon, and a variable third tendon. Direct and indirect tendons converge into a common tendon. The purposes of this study are to add anatomical knowledge about the proximal tendinous complex and describe anatomical variants of the indirect tendon and, on these basis, categorize different anatomical patterns. Method: In this study, 48 hemipelvis from bodies donated to the Universitat Autònoma de Barcelona have been dissected to examine the proximal tendinous complex of the rectus femoris. Results: The following anatomical variants of the indirect tendon were described: inferior aponeurotic expansion in 23/48 cases (47.9%); superior aponeurotic expansion in 21/48 cases (43.7%); and an unusual origin of the myotendinous junction of the rectus femoris in the free portion of the indirect tendon in 19/48 cases (39.6%). On the basis of the aponeurotic expansions, the following anatomical patterns of the indirect tendon were defined: standard (19/48 cases, 39.6%), superior and inferior complex (15/48 cases, 31.2%), inferior complex (8/48 cases, 16.7%), and superior complex (6/48 cases, 12.5%). Conclusion: We can categorize four different anatomical patterns of the indirect tendon, three of which are complex. We suggest that complex patterns can cause an increased stiffness of the indirect tendon and so be considered non-modifiable risk factors for rectus femoris injuries. Finally, it would be useful to identify complex patterns and perform injury prevention actions through specific physical preparation programs. [ABSTRACT FROM AUTHOR]

Teres major injuries are rare and are generally treated conservatively, except in high-performance athletes. This report describes a case of traumatic rupture of the teres major at its myotendinous junction in a professional gymnast. The patient underwent surgical treatment 10 days after the injury. Six months post-surgery, the patient achieved complete recovery of the range of motion and strength, returning to the pre-injury performance level, guided by physiotherapy rehabilitation. This is the first documented case in the literature of surgical treatment of this injury in a professional gymnast. The main lesson from this case is that early surgical repair in elite athletes can result in excellent functional outcomes and allow return to sport at the pre-injury performance level. [ABSTRACT FROM AUTHOR]

Background: Marinesco-Sjögren syndrome (MSS) is an autosomal recessive neuromuscular disorder that arises in early childhood and is characterized by congenital cataracts, myopathy associated with muscle weakness, and degeneration of Purkinje neurons leading to ataxia. About 60% of MSS patients have loss-of-function mutations in the SIL1 gene. Sil1 is an endoplasmic reticulum (ER) protein required for the release of ADP from the master chaperone Bip, which in turn will release the folded proteins. The expression of non-functional Sil1 leads to the accumulation of unfolded proteins in the ER and this triggers the unfolded protein response (UPR). A dysfunctional UPR could be a key element in the pathogenesis of MSS, although our knowledge of the molecular pathology of MSS is still incomplete. Methods: RNA-Seq transcriptomics was analysed using the String database and the Ingenuity Pathway Analysis platform. Fluorescence confocal microscopy was used to study the remodelling of the extracellular matrix (ECM). Transmission electron microscopy (TEM) was used to reveal the morphology of the ECM in vitro and in mouse tendon. Results: Our transcriptomic analysis, performed on patient-derived fibroblasts, revealed 664 differentially expressed (DE) transcripts. Enrichment analysis of DE genes confirmed that the patient fibroblasts have a membrane trafficking issue. Furthermore, this analysis indicated that the extracellular space/ECM and the cell adhesion machinery, which together account for around 300 transcripts, could be affected in MSS. Functional assays showed that patient fibroblasts have a reduced capacity of ECM remodelling, reduced motility, and slower spreading during adhesion to Petri dishes. TEM micrographs of negative-stained ECM samples from these fibroblasts show differences of filaments in terms of morphology and size. Finally, structural analysis of the myotendinous junction of the soleus muscle and surrounding regions of the Achilles tendon revealed a disorganization of collagen fibres in the mouse model of MSS (woozy). Conclusions: ECM alterations can affect the proper functioning of several organs, including those damaged in MSS such as the central nervous system, skeletal muscle, bone and lens. On this basis, we propose that aberrant ECM is a key pathological feature of MSS and may help explain most of its clinical manifestations. [ABSTRACT FROM AUTHOR]

Myofibres serve as the functional unit for locomotion, with the sarcomere as fundamental subunit. Running the entire length of this structure are hundreds of myonuclei, located at the periphery of the myofibre, juxtaposed to the plasma membrane. Myonuclear specialisation and clustering at the centre and ends of the fibre are known to be essential for muscle contraction, yet the molecular basis of this regionalisation has remained unclear. While the 'myonuclear domain hypothesis' helped explain how myonuclei can independently govern large cytoplasmic territories, novel technologies have provided granularity on the diverse transcriptional programs running simultaneously within the syncytia and added a new perspective on how myonuclei communicate. Building upon this, we explore the critical cellular and molecular sources of transcriptional and functional heterogeneity within myofibres, discussing the impact of intrinsic and extrinsic factors on myonuclear programs. This knowledge provides new insights for understanding muscle development, repair, and disease, but also opens avenues for the development of novel and precise therapeutic approaches. [ABSTRACT FROM AUTHOR]

Background: Distal triceps tendon ruptures occur most commonly in middle-aged males, with possible rupture locations including the musculotendinous junction, mid-tendon, or most commonly, at the tendinous insertion. This surgical technique video demonstrates a hybrid distal triceps tendon repair construct utilizing transosseous sutures, SpeedBridge compression, and knotless suture anchor fixation. Indications: Indications for this procedure include an acute injury with complete avulsion of the distal triceps tendon from the olecranon and extension weakness. The goals of surgical repair include restoration of the tendon footprint on the olecranon and the creation of a strong fixation construct that balances tension to optimize healing and restore functional range of motion. Technique Description: The proximal avulsed tendon is prepared with two number 2 suture tapes placed in a locking Krackow fashion. The locking stitch exit point is determined at a distance proximal to the distal end of the tendon to optimize tension after the reduction of the tendon to the footprint. Two looped sutures are then passed through the tendon at the same exit level as the locking stitch, 1 on the medial and lateral sides of the locking stitch, respectively. Two transosseous tunnels are drilled obliquely, from proximal to distal, through the olecranon. A 4.75-mm suture anchor is then drilled and tapped in the proximal ulna, in between 2 transosseous tunnel exit points, for lateral placement. The medial and lateral locked stitches are passed through the medial and lateral transosseous tunnels, respectively. The SpeedBridge construct is formed by passing one suture from each locking stitch limb back through the tendon using the previously placed looped sutures as shuttling devices. After appropriate tensioning, the sutures are secured into the previously drilled 4.75-mm suture anchor in a specific fashion. Results: Current literature suggests that the SpeedBridge technique for triceps tendon repair demonstrates good functional and clinical outcomes with high satisfaction rates, elbow functional scores, and rates of returning to work/activity, coupled with low complication rates. Conclusion: The hybrid SpeedBridge construct is an effective technique for acute distal triceps tendon repair. Patient Consent Disclosure Statement: The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication. [ABSTRACT FROM AUTHOR]

Background: Management of long head of the biceps tendon (LHBT) pathology is accomplished through a biceps tenotomy or tenodesis. While both modalities provide beneficial outcomes, a biceps tenodesis may confer improved cosmesis, functional outcomes, and decreased muscle cramping postoperatively. Many procedural considerations are undertaken prior to a tenodesis, such as the surgical approach and fixation device. While similar clinical outcomes are achieved between an open subpectoral and arthroscopic suprapectoral biceps tenodesis (ASPBT) with interference screw (IS) fixation, the latter technique offers a minimally invasive modality. Indications: The primary indications for an ASPBT include superior labrum anterior posterior (SLAP) tears, LHBT tears, biceps instability, bicipital tunnel disease, biceps pulley lesions, and biceps tenosynovitis. Contraindications to the arthroscopic approach include a distal lesion of the biceps tendon below the pectoralis major tendon (PMT). The IS may be used to create a biomechanically stiffer construct. Technique Description: With the arthroscope in the lateral portal, the distal aspect of the bicipital groove proximal to the superior border of the PMT is identified and opened. The LHBT is subsequently mobilized and released. An anterosuperolateral portal is localized with a spinal needle positioned perpendicular to the bicipital tunnel, 1.5 cm proximal to the superior border of the PMT. The biceps is then removed ex vivo and whip-stitches are sewn beginning 1 cm proximal to the myotendinous junction of the LHBT. After firmly associating the LHBT with the tip of the IS, a guidewire is placed 1.5 cm superior to the superior border of the PMT, perpendicular to the humerus, and a reamer is used to prepare a 6-, 7-, or 8-mm diameter socket. The tendon is inserted through the accessory portal into the tunnel, followed by screw fixation. Suture tails are tied with 5 alternating half hitches, each secured via an arthroscopic knot pusher. Results: ASPBT with IS fixation provides significant pain relief, improves range of motion (ROM), and enhances quality of life. Discussion: ASPBT with IS fixation provides significant improvements in patient-reported and functional outcomes and thus can be an acceptable treatment for LHBT pathology. Patient Consent Disclosure Statement: The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication. [ABSTRACT FROM AUTHOR]

Two primary muscles of the forearm of extensor group are located on the radial side of the wrist, named as the extensor carpi radialis longus (ECRL) muscle and extensor carpi radialis brevis (ECRB) muscle. At the musculotendinous junction, the ECRL and ECRB travel deep to the abductor pollicis longus, extensor pollicis brevis, and extensor pollicis longus muscles and tendons in the hand. The ECRB is covered by the ECRL as it courses distally. An additional tendon slip of the ECRL and from ECRB, respectively, was discovered during dissection of the forearm's extensor compartment and dorsum of the hand with the cadaver in the supine position. The intermedius tendinous slip from ECRL to ECRB originates from the lateral side of ECRL and gets inserted within the same tendinous sheath of the tendon of ECRB, similarly, tendinous slip from ECRB to ECRL originates from the side of ECRB, cross the intermedius slip of ECRL superficially and gets inserted on the base of second metacarpal bone with the tendon of ECRL. [ABSTRACT FROM AUTHOR]

Sports-related muscle injuries account for 10–55% of all injuries, which is a growing concern, especially given the aging world population. To evaluate the process of skeletal muscle injury and compare it with muscle lesions observed in humans, we developed a novel in vivo model in sheep. In this model, muscle injury was induced by an ultrasound-guided transverse biopsy at the myotendinous junction of the medial gastrocnemius muscle. Twelve male sheep were examined at 3, 7, 14, and 28 days post-injury. Histological, immunofluorescence, and MRI analyses indicate that our sheep model could resemble key human clinicopathological features. Statistically significant differences (p < 0.05) were observed in collagen I, dMHC, α-SMA, and CD68 immunohistochemical detection when comparing injured and healthy muscles. The injured gastrocnemius muscle exhibited elevated levels of type I collagen, infiltration of CD68(+) macrophages, angiogenesis, and the emergence of newly regenerated dMHC(+) myofibers, which persisted for up to 4 weeks post-injury. Similarly, the progression of muscle injury in the sheep model was assessed using advanced clinical 3 T MRI and compared with MRI scans from human patients. The data indicate that the sheep muscle injury model presents features similar to those observed in human skeletal muscle injuries. This makes it a valuable large animal model for studying muscle injuries and developing novel therapeutic strategies. [ABSTRACT FROM AUTHOR]

A number of environmental toxicants are noted for their activity that leads to declined motor function. However, the role of muscle as a proximal toxicity target organ for environmental agents has received considerably less attention than the toxicity targets in the nervous system. Nonetheless, the effects of conventional neurotoxicants on processes of myogenesis and muscle maintenance are beginning to resolve a concerted role of muscle as a susceptible toxicity target. A large body of evidence from epidemiological, animal, and in vitro studies has established that methylmercury (MeHg) is a potent developmental toxicant, with the nervous system being a preferred target. Despite its well-recognized status as a neurotoxicant, there is accumulating evidence that MeHg also targets muscle and neuromuscular development as well as contributes to the etiology of motor defects with prenatal MeHg exposure. Here, we summarize evidence for targets of MeHg in the morphogenesis and maintenance of skeletal muscle that reveal effects on MeHg distribution, myogenesis, myotube formation, myotendinous junction formation, neuromuscular junction formation, and satellite cell-mediated muscle repair. We briefly recapitulate the molecular and cellular mechanisms of skeletal muscle development and highlight the pragmatic role of alternative model organisms, Drosophila and zebrafish, in delineating the molecular underpinnings of muscle development and MeHg-mediated myotoxicity. Finally, we discuss how toxicity targets in muscle development may inform the developmental origins of health and disease theory to explain the etiology of environmentally induced adult motor deficits and accelerated decline in muscle fitness with aging. [ABSTRACT FROM AUTHOR]

Acute exposure to hypoxia increases postural sway, but the underlying neurophysiological factors are unclear. Golgi tendon organs (GTOs), located within the musculotendinous junction (MTJ), provide inhibitory signals to plantar flexor muscles that are important for balance control; however, it is uncertain if GTO function is influenced by hypoxia. The aim of this study was to determine how normobaric hypoxia influences lower limb tendon-evoked inhibitory reflexes during upright stance. We hypothesized that tendon-evoked reflex area and duration would decrease during hypoxia, indicating less inhibition of postural muscles compared with normoxia. At baseline (BL; 0.21 fraction of inspired oxygen, FIO2) and at ∼2 (H2) and 4 (H4) h of normobaric hypoxia (0.11 FIO2) in a normobaric hypoxic chamber, 16 healthy participants received electrical musculotendinous stimulation (MTstim) to the MTJ of the left Achilles tendon. The MTstim was delivered as two sets of 50 stimuli while the participant stood on a force plate with their feet together. Tendon-evoked inhibitory reflexes were recorded from the surface electromyogram of the ipsilateral medial gastrocnemius, and center of pressure (CoP) variables were recorded from the force plate. Normobaric hypoxia increased CoP velocity (P ≤ 0.002) but not CoP standard deviation (P ≥ 0.12). Compared with BL, normobaric hypoxia reduced tendon-evoked inhibitory reflex area by 45% at H2 and 53% at H4 (P ≤ 0.002). In contrast, reflex duration was unchanged during hypoxia. The reduced inhibitory feedback from the GTO pathway could likely play a role in the increased postural sway observed during acute exposure to hypoxia. NEW & NOTEWORTHY: The Ib pathway arising from the Golgi tendon organ provides inhibitory signals onto motor neuron pools that modifies force and, hence, postural control. Although hypoxia influences standing balance (increases sway), the underlying mechanisms have yet to be unraveled. Our study identified that tendon-evoked inhibition onto a plantar flexor motoneuron pool is reduced by acute exposure to normobaric hypoxia. This reduction of inhibition may contribute to the hypoxia-related increase in postural sway. [ABSTRACT FROM AUTHOR]

The myotendinous junction (MTJ) is the interface connecting skeletal muscle and tendon tissues. This specialized region represents the bridge that facilitates the transmission of contractile forces from muscle to tendon, and ultimately the skeletal system for the creation of movement. MTJs are, therefore, subject to high stress concentrations, rendering them susceptible to severe, life-altering injuries. Despite the scarcity of knowledge obtained from MTJ formation during embryogenesis, several attempts have been made to engineer this complex interfacial tissue. These attempts, however, fail to achieve the level of maturity and mechanical complexity required for in vivo transplantation. This review summarizes the strategies taken to engineer the MTJ, with an emphasis on how transitioning from static to mechanically inducive dynamic cultures may assist in achieving myotendinous maturity. [ABSTRACT FROM AUTHOR]

The ischial origin of the hamstring musculature is complex. While the conjoint tendon and semimembranosus are commonly discussed and understood by radiologists, there is a lesser-known origin of the semitendinosus along the inferior and medial surface of the ischium in the form of a broad direct muscular connection. This secondary origin is infrequently described in the radiology literature and is a potential pitfall during grading of semitendinosus injuries if the interpreting physician is unaware of its presence. In a proximal hamstring tendon tear, the direct muscular origin of the semitendinosus can be spared, torn along with the conjoint tendon, or remain intact and contribute to a vertical shearing injury of the semitendinosus myotendinous junction. Detailed knowledge of this anatomy and its imaging appearance in the setting of injury enables the reader to correctly diagnose these unique hamstring injuries. [ABSTRACT FROM AUTHOR]

The myotendinous junction (MTJ) is a vulnerable region at the interface of skeletal muscle and tendon that forms an integrated mechanical unit. This study presents a technique for the spatially restrictive co-culture of human embryonic stem cell (hESC)-derived skeletal myocytes and primary tenocytes for two-dimensional modeling of the MTJ. Micropatterned lanes of extracellular matrix and a 2-well culture chamber define the initial regions of occupation. On day 1, both lines occupy less than 20 % of the initially vacant interstitial zone, referred to henceforth as the junction. Myocyte–tenocyte interdigitations are observed by day 7. Immunocytochemistry reveals enhanced organization and alignment of patterned myocyte and tenocyte features, as well as differential expression of multiple MTJ markers. On day 24, electrically stimulated junction myocytes demonstrate negative contractile strains, while positive tensile strains are exhibited by mechanically passive tenocytes at the junction. Unpatterned tenocytes distal to the junction experience significantly decreased strains in comparison to cells at the interface. Unpatterned myocytes have impaired organization and uncoordinated contractile behavior. These findings suggest that this platform is capable of inducing myocyte–tenocyte junction formation and mechanical coupling similar to the native MTJ, showing transduction of force across the cell–cell interface. The myotendinous junction (MTJ) is an integrated structure that transduces force across the muscle-tendon boundary, making the region vulnerable to strain injury. Despite the clinical relevance, previous in vitro models of the MTJ lack the structure and mechanical accuracy of the native tissue and have difficulty transmitting force across the cell–cell interface. This study demonstrates an in vitro model of the MTJ, using spatially restrictive cues to inform human myocyte–tenocyte interactions and architecture. The model expressed MTJ markers and developed anisotropic myocyte–tenocyte integrations that resemble the native tissue and allow for force transduction from contracting myocytes to passive tenocyte regions. As such, this study presents a system capable of investigating development, injury, and pathology in the human MTJ. [Display omitted] [ABSTRACT FROM AUTHOR]

Myotendinous junction (MTJ) injuries are prevalent in clinical practice, yet the treatment approaches are limited to surgical suturing and conservative therapy, exhibiting a high recurrence rate. Current research on MTJ tissue engineering is scarce and lacks in vivo evaluation of repair efficacy. Here, we developed a three-dimensional-printed bioactive fiber-reinforced hydrogel containing mesenchymal stem cells (MSCs) and Klotho for structural and functional MTJ regeneration. In a rat MTJ defect model, the bioactive fiber-reinforced hydrogel promoted the structural restoration of muscle, tendon, and muscle-tendon interface and enhanced the functional recovery of injured MTJ. In vivo proteomics and in vitro cell cultures elucidated the regenerative mechanisms of the bioactive fiber-reinforced hydrogel by modulating oxidative stress and inflammation, thus engineering an optimized microenvironment to support the survival and differentiation of transplanted MSCs and maintain the functional phenotype of resident cells within MTJ tissues, including tendon/muscle cells and macrophages. This strategy provides a promising treatment for MTJ injuries. [ABSTRACT FROM AUTHOR]

Muscle injuries, such as Achilles and quadriceps tendon ruptures, pose a significant challenge in elite sports, accounting for more than 30% of all sports-related injuries. Our primary goal is to investigate the MR imaging characteristics of tendon rupture in sports injuries and their relationship with patients' clinical symptoms. In our retrospective study at Zhejiang University of Traditional Chinese Medicine's Second Affiliated Hospital (Zhejiang Xinhua Hospital), we compared the clinical presentation and MRI results of 106 patients with isolated AT and QT ruptures. In the AT, the enthesis was identified as a common site of bony avulsions (30.2%). In contrast, insertional ruptures were more common in the gastrocnemius heads (69.8% and 66.0%). The low frequency of mid-substance tears (13.2% to 20.8%) demonstrated the central tendon region's inherent tensile strength. The ruptured musculotendinous junctions affected the soleus (20.8%). In QT, bony avulsions play a minor role (5.1% to 11.3%). The patella was the primary site of tears (42.2% - 45.3%), with the Vastus intermedius favoring proximal tears (58.5%). Our examination of AT and QT ruptures across sub-components sheds light on their distinct patterns and the implications for clinical practice in terms of precise diagnosis, personalized treatment, and, ultimately, better patient outcomes for these debilitating injuries. [ABSTRACT FROM AUTHOR]

This article, titled "Hamstring Strains: Classification and Management," provides information on hamstring strain injuries (HSIs) in sports medicine and rehabilitation. The hamstring muscle complex (HMC) consists of several muscles that play a role in extending the hip and flexing the knee. HSIs are commonly "sprint-type" injuries that occur during high-speed running, affecting the proximal long head of the biceps femoris muscle. "Stretch-type" HSIs can also occur with end-range hip flexion and knee extension, typically involving the proximal semimembranosus tendon. The article discusses the grading of HSIs and outlines a 3-phase protocol for nonoperative treatment of Grade I and II HSIs. Grade III HSIs may require surgical repair, with a goal of returning to sport within 4 to 6 months postoperatively. [Extracted from the article]

A new perspective on rotator cuff anatomy has allowed a better understanding of the patterns of the different rotator cuff tears. It is essential for radiologists to be aware of these different patterns of tears and to understand how they might influence treatment and surgical approach. Our objective is to review the arthroscopy correlated magnetic resonance imaging appearance of the different types of rotator cuff tears based on current anatomical concepts. Critical relevance statement Knowledge of the characteristics of rotator cuff tears improves our communication with the surgeon and can also make it easier for the radiologist to prepare a report that guides therapeutic conduct and serves as a prognosis for the patient. Key points • There is no universally accepted classification for RC tears. • New patterns such as delamination or myotendinous junction tears have been defined. • The most difficult feature to assess in full thickness tears on MRI is the pattern. • Fatty infiltration of the RC tendons is crucial in the prognosis and outcome. • The radiological report is an effective way of communication with the surgeon. [ABSTRACT FROM AUTHOR]

Recently, it has become clear that peri-muscular tissues play a significant role in the deterioration of muscle function. Understanding the function and regeneration of muscle, as well as its surrounding tissues, is crucial to determining the causes of muscular illnesses. However, the regeneration process of the myotendinous junction (MTJ), the most closely related peri-muscular tissue, is still unknown. Therefore, we generated a mouse model of MTJ injury by collagenase injection and searched for the process of regeneration of the MTJ and its adjacent regions. The MTJ region was damaged by collagenase injection, which greatly increased the tendon cross sectional area. Collagenase injections increased the proportion of myofibers with a central nucleus, which is a characteristic of regenerating muscle. The collagenase injection group had myofibers with central nuclei and expressing MTJ markers. Additionally, we measured the length of MTJs using serial cross sections of the soleus muscle and discovered that MTJs at 2 weeks after collagenase injection were shorter compared to the control group, with a propensity to progressively recover their length over time. The results showed that MTJs undergo morphological regeneration even when severely damaged, and that this regeneration occurs in conjunction with muscle regeneration. We anticipate that these findings will be valuable in upcoming research on motor unit regeneration. [ABSTRACT FROM AUTHOR]

This article discusses a case report of a gluteus maximus tear in a pickleball player. The gluteus maximus is a large muscle in the buttocks that plays a significant role in hip extension and maintaining posture. The patient experienced left buttock pain and bruising after sustaining an ankle sprain while playing pickleball. Imaging revealed a partial thickness tear of the gluteus maximus muscle. The patient was managed nonoperatively with compression, icing, acetaminophen, and physical therapy, and was able to return to pickleball within four weeks. The article highlights the successful nonoperative management of this type of injury in athletes. [Extracted from the article]

This article discusses a case of a 52-year-old male who presented with sudden onset nausea and vomiting, followed by acute left eye proptosis with redness. The patient also experienced left-sided second, third, fourth, and sixth nerve palsy, along with orbital pain and dimness of vision. After initial evaluation, a diagnosis of idiopathic orbital inflammatory syndrome (OIS) with orbital pseudotumor and orbital myositis was made. The patient was treated with intravenous pulse methylprednisolone and maintained on oral steroids. While the extra-ocular movements resolved completely, the patient's visual acuity remained compromised. OIS is a constellation of multiple idiopathic inflammatory involvement of several sites in the orbit, leading to various manifestations. Treatment typically involves steroids, but refractory cases may require steroid-sparing agents or radiation therapy. [Extracted from the article]

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. [ABSTRACT FROM AUTHOR]

Myostatin (Myo) is known to suppress skeletal muscle growth, and was recently reported to control tendon homeostasis. The purpose of the present study was to investigate the regulatory involvement of Myo in the myotendinous junction (MTJ) in vivo and in vitro. After Achilles tendon injury in mice, we identified unexpected cell accumulation on the tendon side of the MTJ. At postoperative day 7 (POD7), the nuclei had an egg-like profile, whereas at POD28 they were spindle-shaped. The aspect ratio of nuclei on the tendon side of the MTJ differed significantly between POD7 and POD28 (p = 4.67 × 10−34). We then investigated Myo expression in the injured Achilles tendon. At the MTJ, Myo expression was significantly increased at POD28 relative to POD7 (p = 0.0309). To investigate the action of Myo in vitro, we then prepared laminated sheets of myoblasts (C2C12) and fibroblasts (NIH3T3) (a pseudo MTJ model). Myo did not affect the expression of Pax7 and desmin (markers of muscle development), scleraxis and temonodulin (markers of tendon development), or Sox9 (a common marker of muscle and tendon development) in the cell sheets. However, Myo changed the nuclear morphology of scleraxis-positive cells arrayed at the boundary between the myoblast sheet and the fibroblast sheet (aspect ratio of the cell nuclei, myostatin(+) vs. myostatin(-): p = 0.000134). Myo may strengthen the connection at the MTJ in the initial stages of growth and wound healing. [ABSTRACT FROM AUTHOR]

• Specification of ECM at the murine MTJ depended on muscle contraction. • Knockout of Tbx3 resulted in an ectopic muscle that inserted into an MTJ. • Ectopic MTJ formation was not dependent on insertion into an enthesis. • Deposition of ECM at the MTJ was also influenced by static loading. The myotendinous junction (MTJ) contributes to the generation of motion by connecting muscle to tendon. At the adult MTJ, a specialized extracellular matrix (ECM) is thought to contribute to the mechanical integrity of the muscle-tendon interface, but the factors that influence MTJ formation during mammalian development are unclear. Here, we combined 3D imaging and proteomics with murine models in which muscle contractility and patterning are disrupted to resolve morphological and compositional changes in the ECM during MTJ development. We found that MTJ-specific ECM deposition can be initiated via static loading due to growth; however, it required cyclic loading to develop a mature morphology. Furthermore, the MTJ can mature without the tendon terminating into cartilage. Based on these results, we describe a model wherein MTJ development depends on mechanical loading but not insertion into an enthesis. [ABSTRACT FROM AUTHOR]

The myotendinous junction (MTJ) is structurally specialized to transmit force. The highly folded muscle membrane at the MTJ increases the contact area between muscle and tendon and potentially the load tolerance of the MTJ. Muscles with a high content of type II fibers are more often subject to strain injury compared with muscles with type I fibers. It is hypothesized that this is explained by a smaller interface area of MTJ in type II compared with type I muscle fibers. The aim was to investigate by confocal microscopy whether there is difference in the surface area at the MTJ between type I and II muscle fibers. Individual muscle fibers with an intact MTJ were isolated by microscopic dissection in samples from human semitendinosus, and they were labeled with antibodies against collagen XXII (indicating MTJ) and type I myosin (MHCI). Using a spinning disc confocal microscope, the MTJ from each fiber was scanned and subsequently reconstructed to a 3D‐model. The interface area between muscle and tendon was calculated in type I and II fibers from these reconstructions. The MTJ was analyzed in 314 muscle fibers. Type I muscle fibers had a 22% larger MTJ interface area compared with type II fibers (p < 0.05), also when the area was normalized to fiber diameter. By the new method, it was possible to analyze the structure of the MTJ from a large number of human muscle fibers. The finding that the interface area between muscle and tendon is higher in type I compared with type II fibers suggests that type II fibers are less resistant to strain and therefore more susceptible to injury. [ABSTRACT FROM AUTHOR]

Introduction: the objective of this anatomical investigation was to record the morphology of peroneus longus (PL), brevis (PB) and tertius (PT) muscles in human cadaveric specimens. Material and Methods: this study utilized 40 cadaveric formalin fixed lower limb specimens. The leg region was meticulously dissected to expose the muscle belly and their tendons to study the morphology. They were traced till their insertion in the foot. The morphometric data were recorded by using the digital Vernier caliper. Results: PL tendon was inserting to the first metatarsal and medial cuneiform bones in 32 specimens (80%), to the shaft of first metatarsal in 3 cases (7.5%) and in 5 specimens, tendon got inserted into the second metatarsal (12.5%). Thirty PB specimens (75%) had tubular morphology at the insertion and 10 specimens (25%) showed a fan or triangular shaped flattened insertion into the fifth metatarsal. The PT was observed in all of our specimens (100%). It presented a single tendon at the site of insertion in 28 specimens (70%), presented a flattered broad insertion (band like) in 7 specimens (17.5%). This morphology shared a slip to the PB and in 5 specimens (12.5%), the muscle got inserted into the fourth metatarsal and gave fibrous expansion to the extensor digitorum longus. Conclusion: we believe that the morphological data of the peroneal muscles presented in this study are beneficial to the plastic and reconstructive surgeries, ankle and foot surgeries during the muscle flap and correction procedures of the lower extremity. [ABSTRACT FROM AUTHOR]

Recent years have seen the development of various classifications of muscle injuries, primarily based on the topographic location within the bone-tendon–muscle chain. This paper proposes an enhanced nomenclature for muscle injuries that incorporates histoarchitectural definitions alongside topographic classifications, emphasizing the importance of connective tissue damage characterization. A detailed understanding of the distinct anatomical and histological characteristics of tendon, aponeurosis, and fascia is essential for consistent terminology. Tendons, aponeuroses, and fasciae, while all composed of dense connective tissue, differ in collagen fiber orientation and structural organization. Tendons feature longitudinally aligned fibers suited for high tensile forces and muscle-to-bone connections. Aponeuroses have perpendicular collagen fiber layers, allowing for force distribution and support for both longitudinal and transverse traction. Fasciae exhibit loosely organized fibers providing flexibility and movement between muscles. The continuity and differences within the musculotendinous frameworks, particularly at the musculotendinous junction (MTJ), elucidate the higher frequency of injuries at these sites compared with tendons, highlighting the MTJ's role as a stress-absorbing 'safety valve.' [ABSTRACT FROM AUTHOR]

Background: The most common mechanism of injury of muscles is related to muscle strain (indirect muscle injury), mainly in the lower limbs. Muscles are at risk for disruption during eccentric contraction, as the force of active contraction is added to the passive stretching force applied to the myotendinous junction (MTJ). Although clinical examinations remain very important, it has been shown that radiological findings can aid clinicians in the initial assessment. Objective: To evaluate the accuracy and specificity of high frequency ultrasound in identification and characterization of acute and chronic muscle injuries in comparison with MRI. Methods: This ultrasonography & cross sectional study was done in private radiological centers with a period of 24 months on a random sample of 30 patients. Our study included 30 patients complaining of traumatic acute and chronic muscle injuries, 26 males (86.7%) and 4 females (13.3%), ranging in age from 18 to 55 years with a mean age of 37.5 years. Results: The accuracy, sensitivity & specificity of ultrasound in detecting all muscle injuries in comparison to MRI: 86.7%, 87.5% & 83.3% respectively. The accuracy, sensitivity & specificity of ultrasound in detecting acute muscle injuries in comparison to MRI: 66.7%, 66.7 % & 66.7% respectively. The accuracy, sensitivity & specificity of ultrasound in detecting chronic muscle injuries in comparison to MRI: 95.2%, 94.4% & 100% respectively. Conclusion: Ultrasound is highly operator dependent, useful for diagnosis of chronic muscle injury in comparison to the MRI, yet with pitfalls in acute muscle injuries, yet the ultrasound classification criteria for muscle injury can be used to predict the severity of injury and guide decision on the type of treatment and MRI is still considered the main diagnostic tool for muscle injuries and classification. [ABSTRACT FROM AUTHOR]

In the musculoskeletal system, the myotendinous junction (MTJ) is optimally designed from the aspect of force transmission generated from a muscle through a tendon onto the bone to induce movement. Although the MTJ is a key complex tissue in force transmission, the realistic fabrication, and formation of complex tissues can be limited. To obtain the MTJ construct, we prepared two bioinks, muscle‐ and tendon‐derived decellularized extracellular matrix (dECM), which can induce myogenic and tenogenic differentiation of human adipose‐derived stem cells (hASCs). By using a modified bioprinting process supplemented with a nozzle consisting of a single‐core channel and double‐sheath channels, we can achieve three different types of MTJ units, composed of muscle, tendon, and interface zones. Our results indicated that the bioprinted dECM‐based constructs induced hASCs to myogenic and tenogenic differentiation. In addition, a significantly higher MTJ‐associated gene expression was detected at the MTJ interface with a cell‐mixing zone than in the other interface models. Based on the results, the bioprinted MTJ model can be a potential platform for understanding the interaction between muscle and tendon cells, and even the bioprinting method can be extensively applied to obtain complex tissues. [ABSTRACT FROM AUTHOR]

The myotendinous junction (MTJ), a specialized interface for force transmission between muscle and tendon, has a unique transcriptional activity and is highly susceptible to muscle strain injury. Eccentric exercise training is known to reduce this risk of injury, but knowledge of the influence of exercise on the MTJ at the molecular and cellular levels is limited. In this study, 30 subjects were randomized to a single bout of eccentric exercise 1 week prior to tissue sampling (exercised) or no exercise (control). Samples were collected from the semitendinosus as part of reconstruction of the anterior cruciate ligament and divided into fractions containing muscle, MTJ and tendon, respectively. The concentrations of macrophages and satellite cells were counted, and the expression of genes previously known to be active at the MTJ were analyzed by real-time–quantitative PCR. An effect of the single bout of exercise was found on the expression of nestin (NES) and osteocrin (OSTN) mRNA in the MTJ and tendon fractions. Genes earlier identified at the MTJ (COL22A1, POSTN, ADAMTS8, MNS1, NCAM1) were confirmed to be expressed at a significantly higher level in the MTJ compared to muscle and tendon but were unaffected by exercise. In the exercise group a higher concentration of macrophages, but not of satellite cells, was seen in muscle close to the MTJ. The expression of NES and OSTN was higher in human semitendinosus MTJ 1 week after a single session of heavy eccentric exercise. Based on these results, NES and OSTN could have a part in explaining how the MTJ adapts to eccentric exercise. [ABSTRACT FROM AUTHOR]

The surgical fixation of an acute on chronic pectoralis major rupture with inciting injury 7 years prior has never been reported in the literature. Thus, we report the first case of an acute on chronic pectoralis major rupture repair in an active male patient who underwent successful surgical intervention and review the pathophysiology and treatment of pectoralis major tears. [ABSTRACT FROM AUTHOR]

The morphology of the more superficial tissue of the human tongue was investigated and discussed with the clinical appearance of fissures. Three regions could be distinguished according to the presence and shape of the aponeurosis linguae: the central region showed a thick aponeurotic plate with myotendinous muscle fibre insertions. The lateral region showed still an aponeurosis linguae but of reduced thickness and without muscle insertions. The edge‐wise and lower region showed no aponeurosis linguae but a fatty subcutis and myocutaneous muscle fibre insertions lacking specific molecules of myotendinous junctions. This system of partially developed exoskeleton seems to underlie but not to be involved in tongue fissures, which are more superficial within the epidermis and dermis. [ABSTRACT FROM AUTHOR]

• Collagen XXII is the unique extracellular matrix marker of the myotendinous junction. • CRISPR/Cas9-mediated col22a1 gene knockout in zebrafish results in loss of the myotendinous unit integrity and dysfunctions in force transmission but with phenotypic variability • A subset of the col22a1 −/− progeny displays severe phenotype accompanied with erratic movements and postural defects and dies before metamorphosis • The moderate col22a1 −/− phenotype is characterized by muscle fatigue and mitochondrial adaptation to exercise in adults. • COL22A1 represents a novel candidate gene for human myopathies characterized by muscle weakness and dysfunctional force transmission. The myotendinous junction (MTJ) is essential for the integrity of the musculoskeletal unit. Here, we show that gene ablation of the MTJ marker col22a1 in zebrafish results in MTJ dysfunction but with variable degrees of expression and distinct phenotypic classes. While most individuals reach adulthood with no overt muscle phenotype (class 1), a subset of the progeny displays severe movement impairment and die before metamorphosis (class 2). Yet all mutants display muscle weakness due to ineffective muscle force transmission that is ultimately detrimental for class-specific locomotion-related functions. Movement impairment at the critical stage of swimming postural learning causes class 2 larval death by compromising food intake. In class 1 adults, intensive exercise is required to uncover a decline in muscle performance, accompanied by higher energy demand and mitochondrial adaptation. This study underscores COL22A1 as a candidate gene for myopathies associated with dysfunctional force transmission and anticipates a phenotypically heterogeneous disease. [ABSTRACT FROM AUTHOR]

Owing to a rapid increase in aging population in recent years, the deterioration of motor function in older adults has become an important social problem, and several studies have aimed to investigate the mechanisms underlying muscle function decline. Furthermore, structural maintenance of the muscle–tendon–bone complexes in the muscle attachment sites is important for motor function, particularly for joints; however, the development and regeneration of these complexes have not been studied thoroughly and require further elucidation. Recent studies have provided insights into the roles of mesenchymal progenitors in the development and regeneration of muscles and myotendinous junctions. In particular, studies on muscles and myotendinous junctions have—through the use of the recently developed scRNA-seq—reported the presence of syncytia, thereby suggesting that fibroblasts may be transformed into myoblasts in a BMP-dependent manner. In addition, the high mobility group box 1—a DNA-binding protein found in nuclei—is reportedly involved in muscle regeneration. Furthermore, studies have identified several factors required for the formation of locomotor apparatuses, e.g., tenomodulin (Tnmd) and mohawk (Mkx), which are essential for tendon maturation. [ABSTRACT FROM AUTHOR]

Background. Animal models of muscle injury have primarily relied on methods which do not mimic the chronic scarring that typically occurs adjacent to the myotendinous junction (MTJ). The goal of this study was three-fold: (i) to create a strain-induced in vivo model of rectus femoris MTJ injury in rats; (ii) to document clinical manifestations of injury using longitudinal tracking of individual animals via voluntary and compulsory (treadmill) mobility analyses and (iii) to validate and assess the model for persistent scarring through serial histologic assessment and development of a semi-quantitative grading scheme to characterize injury response over time. Methods. Strain-induced MTJ injury was generated in male Sprague Dawley rats via needle tension directed along the transverse axis between the rectus femoris muscle and distal tendon that attaches to the patella. Animals received mobility assessments (gait analysis using a DigiGait Treadmill System and weight bearing using a Tekscan Rodent Walkway System) at days 0, 1, 3, 6, 13, 20, and 27 of the experimental protocol. Rats were euthanized at 1, 3, 7, 14, and 28 days post-injury (n = 6 rats per time-point) and hindlimbs were processed for histology. Results. Significant changes in locomotor parameters included injured and contralateral limb paw area, max dA/dt (limb deceleration/breaking time), stride time, stance time, force time impulse, and fore/hind symmetry, and injured limb maximum force. The most significant and consistent histologic finding was a pathologic fibrotic adhesive lesion at the muscle and tendon interface along the proximal aspect of the patella just distal to the injury site. This lesion was composed of reactive fibroblasts, disorganized collagen fibers, vascular profiles, and a myxomatous ground substance stroma. Conclusions. This work is the first to characterize the clinical and pathologic development of a chronic model of rectus femoris MTJ injury, which resulted in altered mobility likely caused by a strain-induced fibrotic scar along the anterior patella. Notably, both the functional and pathologic changes recapitulated the course of injury progression similar to what is described in humans. This work provides a unique model to study MTJ injury mechanisms for the identification of enhanced treatment options for patients who suffer from activity-related muscle conditions. [ABSTRACT FROM AUTHOR]

Tendons are extracellular matrix (ECM)-rich structures that mediate muscle attachments with the skeleton, but surprisingly little is known about molecular mechanisms of attachment. Individual myofibers and tenocytes in Drosophila interact through integrin (Itg) ligands such as Thrombospondin (Tsp), while vertebrate muscles attach to complex ECM fibrils embedded with tenocytes. We show for the first time that a vertebrate thrombospondin, Tsp4b, is essential for muscle attachment and ECM assembly at myotendinous junctions (MTJs). Tsp4b depletion in zebrafish causes muscle detachment upon contraction due to defects in laminin localization and reduced Itg signaling at MTJs. Mutation of its oligomerization domain renders Tsp4b unable to rescue these defects, demonstrating that pentamerization is required for ECM assembly. Furthermore, injected human TSP4 localizes to zebrafish MTJs and rescues muscle detachment and ECM assembly in Tsp4b-deficient embryos. Thus Tsp4 functions as an ECM scaffold at MTJs, with potential therapeutic uses in tendon strengthening and repair.