Abstract Despite the importance of cell fusion for mammalian development and physiology, factors critical this process remain to be fully defined, which has severely limited our ability reconstitute fusion. Myomaker ( Tmem8c ) is a muscle-specific protein required myoblast Expression myomaker in fibroblasts drives their with myoblasts, but not other myomaker-expressing fibroblasts, highlighting requirement additional myoblast-derived Here we show that Gm7325 , name myomerger, induces...

Fusion of skeletal muscle stem/progenitor cells is required for proper development and regeneration, however the significance this process during adult hypertrophy has not been explored. In response to overload after synergist ablation in mice, we show that myomaker, a specific membrane protein essential myoblast fusion, activated mainly progenitors myofibers. We rendered fusion-incompetent through genetic deletion myomaker stem observed complete reduction overload-induced hypertrophy. This...

Skeletal muscle adapts to external stimuli such as increased work. Muscle progenitors (MPs) control repair due severe damage, but the role of MP fusion and associated myonuclear accretion during exercise are unclear. While we previously demonstrated that is required for growth using a supra-physiological model (Goh Millay, 2017), questions remained about need accrual adaptation in physiological setting. Here, developed an 8 week high-intensity interval training (HIIT) protocol assessed...

The purpose of this study was to examine the independent and combined effects carbohydrate caffeine ingestion on performance various physiological parameters during aerobic cycling (∼1 h). Ten male cyclists (28 ± 9 years, 73 6 kg, 66 mL·kg(-1)·min(-1) maximal oxygen consumption) performed 20 min steady-state (SS) (60% peak power (W(max))) followed by a simulated 20-km time trial (TT) under placebo (PLA), (CHO), (CAF), CAF-CHO conditions, all which were in fed state. improved TT 3.4% 2% (84...

The effects of different carbohydrate-protein (CHO + Pro) beverages were compared during recovery from cycling exercise. Twelve male cyclists (VO2peak: 65 ± 7 mL/kg/min) completed ~1 h high-intensity intervals (EX1). Immediately and 120 min following EX1, subjects consumed one three calorically-similar (285–300 kcal) in a cross-over design: carbohydrate-only (CHO; 75 g per beverage), high-carbohydrate/low-protein (HCLP; 45 CHO, 25 Pro, 0.5 fat), or low-carbohydrate/high-protein (LCHP; 8 55 4...

Muscle contractures are a prominent and disabling feature of many neuromuscular disorders, including the 2 most common forms childhood neurologic dysfunction: neonatal brachial plexus injury (NBPI) cerebral palsy. There currently no treatment strategies to directly alter contracture pathology, as pathogenesis these is unknown. We previously showed in mouse model NBPI that result from impaired longitudinal muscle growth. Current presumed explanations for growth impairment focus on...

Background: Contractures following neonatal brachial plexus injury (NBPI) are associated with growth deficits in denervated muscles. This impairment is mediated by an increase muscle protein degradation, as contractures can be prevented NBPI mouse model bortezomib (BTZ), a proteasome inhibitor (PI). However, BTZ treatment causes substantial toxicity (0% to 80% mortality). The current study tested the hypothesis that newer-generation PIs prevent less severe than BTZ. Methods: Unilateral...

We previously reported that leukocyte specific β2 integrins contribute to hypertrophy after muscle overload in mice. Because intercellular adhesion molecule-1 (ICAM-1) is an important ligand for integrins, we examined ICAM-1 expression by murine skeletal cells and its contribution the ensuing hypertrophic response. Myofibers control muscles of wild type mice cultures (primary C2C12) did not express ICAM-1. Overload plantaris caused myofibers satellite cells/myoblasts Increased occurred via a...

Brachial plexus birth injury (BPBI) and cerebral palsy (CP) both cause disabling contractures for which no curative treatments exist, largely because contracture pathophysiology is incompletely understood. The distinct neurologic nature of BPBI CP suggest different potential etiologies, although imbalanced muscle strength insufficient length have been variably implicated. current study directly compares the phenotype elbow flexion in human subjects with to test hypothesis that conditions...

Neonatal brachial plexus injury (NBPI) causes disabling and incurable muscle contractures that are driven by impaired growth of denervated muscles. A rare form NBPI, which maintains afferent innervation despite motor denervation, does not cause contractures. As regulates various aspects skeletal homeostasis through NRG/ErbB signaling, our current study investigated the role this pathway in modulating contracture development. Through pharmacologic modification with an ErbB antagonist NRG1...

Neonatal brachial plexus injury (NBPI) causes disabling and incurable contractures, or limb stiffness, which result from proteasome-mediated protein degradation impairing the longitudinal growth of neonatally denervated muscles. We recently showed in a mouse model that 20S proteasome inhibitor, bortezomib, prevents contractures after NBPI. Given uniquely follow neonatal denervation, current study tests hypothesis inhibition during finite window development can prevent long-term contracture...

Neonatal brachial plexus injury (NBPI), a leading cause of pediatric upper limb paralysis, results in disabling and incurable muscle contractures that are driven by impaired longitudinal growth denervated muscles. A rare form NBPI, which maintains both afferent sympathetic innervation despite motor denervation, protects against contractures. We have previously ruled out role for NRG/ErbB signaling, the predominant pathway governing antegrade neuromuscular transmission, modulating formation...

ABSTRACT Introduction : We investigated the extent to which intercellular adhesion molecule‐1 (ICAM‐1), a critical protein of inflammatory response, is expressed in skeletal muscles mdx mice (a murine model Duchenne muscular dystrophy). Methods Muscles were collected from control and at 2‐24 weeks age analyzed for ICAM‐1 expression by means Western blot immunofluorescence. Results revealed higher compared with through 24 age. In contrast muscles, was on membrane damaged, regenerating, normal...

Neonatal brachial plexus injury (NBPI) causes disabling and incurable muscle contractures that result from impaired longitudinal growth of denervated muscles. This deficit in is driven by increased proteasome-mediated protein degradation, suggesting a dysregulation proteostasis. The myostatin (MSTN) pathway, prominent muscle-specific regulator proteostasis, putative signaling mechanism which neonatal denervation could impair growth, thus potential target to prevent NBPI-induced contractures....

Pediatric orthopedic surgeons are frequently confronted with musculoskeletal contractures caused by pediatric neuromuscular conditions, including brachial plexus birth injury (BPBI). These substantially limit function and quality of life in affected children, lead to skeletal dysplasia dislocations. However, existing treatments for these do not restore normal as they fail address the underlying contracture pathophysiology, which remains largely unknown. Over past decade, a wealth scientific...

Abstract Despite the importance of cell fusion for mammalian development and physiology, factors critical this process remain to be fully defined 1 . This lack knowledge has severely limited our ability reconstitute fusion, which is necessary decipher biochemical mechanisms driving plasma membrane merger. Myomaker ( Tmem8c ) a muscle-specific protein required myoblast 2,3 Expression myomaker in fibroblasts drives their with myoblasts, but not other myomaker-fibroblasts, highlighting...

Duchenne muscular dystrophy (DMD) is an X‐linked inherited disease resulting from the absence of cytoskeletal protein dystrophin in skeletal and cardiac muscle cells. Without dystrophin, muscles incur repeated cycles damage regeneration. In a murine model DM (i.e. mdx mice), myeloid cells (neutrophils macrophages) contribute to onset progression DMD. The objective this investigation was determine if intercellular adhesion molecule‐1 (ICAM‐1), inflammatory response, expressed by myofibers...

Recent investigations by our laboratory demonstrated that skeletal muscle cell expression of intercellular adhesion molecule‐1 (ICAM‐1), an important protein the inflammatory response, augmented events myogenesis in which myotubes are forming, adding nuclei, aligning, fusing, synthesizing proteins, and hypertrophying. Our current work extended these findings incorporating pharmacological tools with vitro approach to discern underlying mechanisms associated ICAM‐1 mediated myogenesis....

We previously reported that intercellular adhesion molecule‐1 (ICAM‐1), an important protein of the inflammatory response, was expressed by satellite cells and myofibers hypertrophying muscles. As skeletal muscle cell expression ICAM‐1 contributed to formation regenerating fibers, as well hypertrophy mechanical overload, we speculate facilitates myogenesis. Therefore, purpose current study establish phenotypic alterations associated with ICAM‐1. Through stable transfection C2C12 myoblasts...

PURPOSE: The present study assessed the consistency of repeated time-trials utilizing a computer-simulated cycle ergometer. In addition, we examined associations between power output and trial times (calculated using proprietary software). METHODS: Ten male cyclists (28±8 y, 73.2±5.9 kg, 65.5±9.2 ml/kg/min) completed three cycling trials, separated by 5-14 days each. Each included 20 min at 60% Wmax, followed immediately simulated km time-trial. initial 15 was relatively flat final 5 uphill...