Thyroid hormone receptor α in skeletal muscle is essential for T3-mediated increase in energy expenditure.

Thyroid hormones are important for homeostatic control of energy metabolism and body temperature. Although skeletal muscle is considered a key site for thyroid action, the contribution of thyroid hormone receptor signaling in muscle to whole-body energy metabolism and body temperature has not been resolved. Here, we show that T3-induced increase in energy expenditure requires thyroid hormone receptor alpha 1 (TRα1 ) in skeletal muscle, but that T3-mediated elevation in body temperature is achieved in the absence of muscle-TRα1 . In slow-twitch soleus muscle, loss-of-function of TRα1 (TRαHSACre ) alters the fiber-type composition toward a more oxidative phenotype. The change in fiber-type composition, however, does not influence the running capacity or motivation to run. RNA-sequencing of soleus muscle from WT mice and TRαHSACre mice revealed differentiated transcriptional regulation of genes associated with muscle thermogenesis, such as sarcolipin and UCP3, providing molecular clues pertaining to the mechanistic underpinnings of TRα1 -linked control of whole-body metabolic rate. Together, this work establishes a fundamental role for skeletal muscle in T3-stimulated increase in whole-body energy expenditure.

Abundant Synthesis of Netrin-1 in Satellite Cell-Derived Myoblasts Isolated from EDL Rather Than Soleus Muscle Regulates Fast-Type Myotube Formation.

Resident myogenic stem cells (satellite cells) are attracting attention for their novel roles in myofiber type regulation. In the myogenic differentiation phase, satellite cells from soleus muscle (slow fiber-abundant) synthesize and secrete higher levels of semaphorin 3A (Sema3A, a multifunctional modulator) than those derived from extensor digitorum longus (EDL; fast fiber-abundant), suggesting the role of Sema3A in forming slow-twitch myofibers. However, the regulatory mechanisms underlying fast-twitch myotube commitment remain unclear. Herein, we focused on netrin family members (netrin-1, -3, and -4) that compete with Sema3A in neurogenesis and osteogenesis. We examined whether netrins affect fast-twitch myotube generation by evaluating their expression in primary satellite cell cultures. Initially, netrins are upregulated during myogenic differentiation. Next, we compared the expression levels of netrins and their cell membrane receptors between soleus- and EDL-derived satellite cells; only netrin-1 showed higher expression in EDL-derived satellite cells than in soleus-derived satellite cells. We also performed netrin-1 knockdown experiments and additional experiments with recombinant netrin-1 in differentiated satellite cell-derived myoblasts. Netrin-1 knockdown in myoblasts substantially reduced fast-type myosin heavy chain (MyHC) expression; exogenous netrin-1 upregulated fast-type MyHC in satellite cells. Thus, netrin-1 synthesized in EDL-derived satellite cells may promote myofiber type commitment of fast muscles.

PERK regulates skeletal muscle mass and contractile function in adult mice.

Skeletal muscle mass is regulated by the coordinated activation of several anabolic and catabolic pathways. The endoplasmic reticulum (ER) is a major site of protein folding and a reservoir for calcium ions. Accretion of misfolded proteins or depletion in calcium concentration causes stress in the ER, which leads to the activation of a signaling network known as the unfolded protein response (UPR). In the present study, we investigated the role of the protein kinase R-like endoplasmic reticulum kinase (PERK) arm of the UPR in the regulation of skeletal muscle mass and function in naive conditions and in a mouse model of cancer cachexia. Our results demonstrate that the targeted inducible deletion of PERK reduces skeletal muscle mass, strength, and force production during isometric contractions. Deletion of PERK also causes a slow-to-fast fiber type transition in skeletal muscle. Furthermore, short hairpin RNA-mediated knockdown or pharmacologic inhibition of PERK leads to atrophy in cultured myotubes. While increasing the rate of protein synthesis, the targeted deletion of PERK leads to the increased expression of components of the ubiquitin-proteasome system and autophagy in skeletal muscle. Ablation of PERK also increases the activation of calpains and deregulates the gene expression of the members of the FGF19 subfamily. Furthermore, the targeted deletion of PERK increases muscle wasting in Lewis lung carcinoma tumor-bearing mice. Our findings suggest that the PERK arm of the UPR is essential for the maintenance of skeletal muscle mass and function in adult mice.-Gallot, Y. S., Bohnert, K. R., Straughn, A. R., Xiong, G., Hindi, S. M., Kumar, A. PERK regulates skeletal muscle mass and contractile function in adult mice.

Absence of an aging-related increase in fiber type grouping in athletes and non-athletes.

The aging-related loss of muscle mass is thought to be partly attributable to motor neuron loss and motor unit remodeling that result in fiber type grouping. We examined fiber type grouping in 19- to 85-year-old athletes and non-athletes and evaluated to which extent any observed grouping is explained by the fiber type composition of the muscle. Since regular physical activity may stimulate reinnervation, we hypothesized that fiber groups are larger in master athletes than in age-matched non-athletes. Fiber type grouping was assessed in m. vastus lateralis biopsies from 22 young (19-27 years) and 35 healthy older (66-82 years) non-athletes, and 14 young (20-29 years), 51 middle-aged (38-65 years), and 31 older (66-85 years) athletes. An "enclosed fiber" was any muscle fiber of a particular type surrounded by fibers of the same type only. A fiber type group was defined as a group of fibers with at least one enclosed fiber. Only type II fiber cross-sectional area (FCSA) showed an age-related decline that was greater in athletes (P < .001) than in non-athletes (P = .012). There was no significant age-related effect on fiber group size or fiber group number in athletes or non-athletes, and the observed grouping was similar to that expected from the fiber type composition. At face value, these observations do 1) neither show evidence for an age-related loss and remodeling of motor units nor 2) improved reinnervation with regular physical activity, but 3) histological examination may not reveal the full extent of aging-related motor unit remodeling.

Restricting calcium currents is required for correct fiber type specification in skeletal muscle.

Skeletal muscle excitation-contraction (EC) coupling is independent of calcium influx. In fact, alternative splicing of the voltage-gated calcium channel CaV1.1 actively suppresses calcium currents in mature muscle. Whether this is necessary for normal development and function of muscle is not known. However, splicing defects that cause aberrant expression of the calcium-conducting developmental CaV1.1e splice variant correlate with muscle weakness in myotonic dystrophy. Here, we deleted CaV1.1 (Cacna1s) exon 29 in mice. These mice displayed normal overall motor performance, although grip force and voluntary running were reduced. Continued expression of the developmental CaV1.1e splice variant in adult mice caused increased calcium influx during EC coupling, altered calcium homeostasis, and spontaneous calcium sparklets in isolated muscle fibers. Contractile force was reduced and endurance enhanced. Key regulators of fiber type specification were dysregulated and the fiber type composition was shifted toward slower fibers. However, oxidative enzyme activity and mitochondrial content declined. These findings indicate that limiting calcium influx during skeletal muscle EC coupling is important for the secondary function of the calcium signal in the activity-dependent regulation of fiber type composition and to prevent muscle disease.

Fiber Type Composition and Rate of Force Development in Endurance- and Resistance-Trained Individuals.

Methenitis, S, Spengos, K, Zaras, N, Stasinaki, A-N, Papadimas, G, Karampatsos, G, Arnaoutis, G, and Terzis, G. Fiber type composition and rate of force development in endurance- and resistance-trained individuals. J Strength Cond Res 33(9): 2388-2397, 2019-The purpose of the study was to investigate the relationship between muscle fiber composition and the rate of force development (RFD) in well-trained individuals with different training background. Thirty-eight young men with different training background participated: 9 endurance runners, 10 power-trained individuals, 9 strength-trained individuals, and 10 sedentary individuals. They performed maximal isometric leg press for the measurement of RFD. Body composition (dual x-ray absorptiometry) and vastus lateralis fiber type composition were also evaluated. When all participants were examined as a group, moderate correlations were found between the percent of type II muscle fibers and RFD between 100 and 600 milliseconds (r = 0.321-0.497; p ≤ 0.05). The correlation coefficients were higher for the cross-sectional area (CSA) and the %CSA of type II and IIx muscle fibers (r = 0.599-0.847; p < 0.001). For the power group, RFD up to 250 milliseconds highly correlated with % type IIx muscle fibers and type IIx fiber CSA (r = 0.670-0.826; p ≤ 0.05), as well as with %CSA of type IIx fibers (r = 0.714-0.975; p ≤ 0.05). Significant correlations were found between the relative RFD (·kg lower extremities lean mass) and CSA-%CSA of type II and IIx fibers for the power group (r = 0.676-0.903; p ≤ 0.05). No significant correlations were found between muscle morphology and RFD for the other groups. In conclusion, the present data suggest that there is a strong link between the type IIx muscle fibers and early RFD and relative RFD in power-trained participants. Type II fibers seem to be moderately linked with RFD in non-power-trained individuals.

Three DNA Polymorphisms Previously Identified as Markers for Handgrip Strength Are Associated With Strength in Weightlifters and Muscle Fiber Hypertrophy.

Grishina, EE, Zmijewski, P, Semenova, EA, Cieszczyk, P, Huminska-Lisowska, K, Michalowska-Sawczyn, M, Maculewicz, E, Crewther, B, Orysiak, J, Kostryukova, ES, Kulemin, NA, Borisov, OV, Khabibova, SA, Larin, AK, Pavlenko, AV, Lyubaeva, EV, Popov, DV, Lysenko, EA, Vepkhvadze, TF, Lednev, EM, Bondareva, EA, Erskine, RM, Generozov, EV, and Ahmetov, II. Three DNA polymorphisms previously identified as markers for handgrip strength are associated with strength in weightlifters and muscle fiber hypertrophy. J Strength Cond Res 33(10): 2602-2607, 2019-Muscle strength is a highly heritable trait. So far, 196 single nucleotide polymorphisms (SNPs) associated with handgrip strength have been identified in 3 genome-wide association studies. The aim of our study was to validate the association of 35 SNPs with strength of elite Russian weightlifters and replicate the study in Polish weightlifters. Genotyping was performed using micro-array analysis or real-time polymerase chain reaction. We found that the rs12055409 G-allele near the MLN gene (p = 0.004), the rs4626333 G-allele near the ZNF608 gene (p = 0.0338), and the rs2273555 A-allele in the GBF1 gene (p = 0.0099) were associated with greater competition results (total lifts in snatch and clean and jerk adjusted for sex and weight) in 53 elite Russian weightlifters. In the replication study of 76 sub-elite Polish weightlifters, rs4626333 GG homozygotes demonstrated greater competition results (p = 0.0155) and relative muscle mass (p = 0.046), adjusted for sex, weight, and age, compared with carriers of the A-allele. In the following studies, we tested the hypotheses that these SNPs would be associated with skeletal muscle hypertrophy and handgrip strength. We found that the number of strength-associated alleles was positively associated with fast-twitch muscle fiber cross-sectional area in the independent cohort of 20 male power athletes (p = 0.021) and with handgrip strength in 87 physically active individuals (p = 0.015). In conclusion, by replicating previous findings in 4 independent studies, we demonstrate that the rs12055409 G-, rs4626333 G-, and rs2273555 A-alleles are associated with higher levels of strength, muscle mass, and muscle fiber size.

Correlation of Fiber-Type Composition and Sprint Performance in Youth Soccer Players.

Metaxas, T, Mandroukas, A, Michailidis, Y, Koutlianos, N, Christoulas, K, and Ekblom, B. Correlation of fiber-type composition and sprint performance in youth soccer players. J Strength Cond Res 33(10): 2629-2634, 2019-The aim of this study was to examine the correlation between muscle fiber type and sprint performance in elite young soccer players of different age groups of the same team. Twenty-eight young players participated in this study (group U15, n = 8; group U13, n = 9; and group U11, n = 11). Anthropometric assessments, acceleration (10 m), and Bangsbo modified sprint test (30 m) were performed. Muscle biopsies were obtained from the vastus lateralis, and after that, fiber-type composition was determined by immunohistochemistry. No significant correlations were found between the sprint test and muscle fiber distribution for the groups U13 and U11 (p > 0.05). Also, no correlations were found between cross-sectional areas in the types of fibers with the sprint test in all groups (p > 0.05). A positive correlation was found between type I fibers and the performance in the acceleration test (10 m) (r = 0.77, p < 0.05) was found only in group U15 and a negative correlation between type IIA fibers and the performance in the acceleration test (10 m) (r = -0.89, p < 0.05). The correlations were observed only in group U15, which may indicate that the duration and the intensity of the soccer systematic training can affect the plasticity of the muscle fibers. Specific soccer training in youth is one of the factors that can affect fiber-type plasticity. The specific training programs and status of U15 are more intensive, and the exercises are oriented more to improve physical fitness.

Myomaker is required for the fusion of fast-twitch myocytes in the zebrafish embryo.

During skeletal muscle development, myocytes aggregate and fuse to form multinucleated muscle fibers. Inhibition of myocyte fusion is thought to significantly derail the differentiation of functional muscle fibers. Despite the purported importance of fusion in myogenesis, in vivo studies of this process in vertebrates are rather limited. Myomaker, a multipass transmembrane protein, has been shown to be the first muscle-specific fusion protein essential for myocyte fusion in the mouse. We have generated loss-of-function alleles in zebrafish myomaker, and found that fusion of myocytes into syncytial fast-twitch muscles was significantly compromised. However, mutant myocytes could be recruited to fuse with wild-type myocytes in chimeric embryos, albeit rather inefficiently. Conversely, overexpression of Myomaker was sufficient to induce hyperfusion among fast-twitch myocytes, and it also induced fusion among slow-twitch myocytes that are normally fusion-incompetent. In line with this, Myomaker overexpression also triggered fusion in another myocyte fusion mutant compromised in the function of the junctional cell adhesion molecule, Jam2a. We also provide evidence that Rac, a regulator of actin cytoskeleton, requires Myomaker activity to induce fusion, and that an approximately 3kb of myomaker promoter sequence, with multiple E-box motifs, is sufficient to direct expression within the fast-twitch muscle lineage. Taken together, our findings underscore a conserved role for Myomaker in vertebrate myocyte fusion. Strikingly, and in contrast to the mouse, homozygous myomaker mutants are viable and do not exhibit discernible locomotory defects. Thus, in the zebrafish, myocyte fusion is not an absolute requirement for skeletal muscle morphogenesis and function.

Transcript profile distinguishes variability in human myogenic progenitor cell expansion capacity.

Primary human muscle progenitor cells (hMPCs) are commonly used to understand skeletal muscle biology, including the regenerative process. Variability from unknown origin in hMPC expansion capacity occurs independently of disease, age, or sex of the donor. We sought to determine the transcript profile that distinguishes hMPC cultures with greater expansion capacity and to identify biological underpinnings of these transcriptome profile differences. Sorted (CD56+/CD29+) hMPC cultures were clustered by unbiased, K-means cluster analysis into FAST and SLOW based on growth parameters (saturation density and population doubling time). FAST had greater expansion capacity indicated by significantly reduced population doubling time (-60%) and greater saturation density (+200%), nuclei area under the curve (AUC, +250%), and confluence AUC (+120%). Additionally, FAST had fewer % dead cells AUC (-44%, P < 0.05). RNA sequencing was conducted on RNA extracted during the expansion phase. Principal component analysis distinguished FAST and SLOW based on the transcript profiles. There were 2,205 differentially expressed genes (DEgenes) between FAST and SLOW (q value ≤ 0.05); 362 DEgenes met a more stringent cut-off (q value ≤ 0.001 and 2.0 fold-change). DEgene enrichment suggested FAST (vs. SLOW) had promotion of the cell cycle, reduced apoptosis and cellular senescence, and enhanced DNA replication. Novel (RABL6, IRGM1, and AREG) and known (FOXM1, CDKN1A, Rb) genes emerged as regulators of identified functional pathways. Collectively the data suggest that variation in hMPC expansion capacity occurs independently of age and sex and is driven, in part, by intrinsic mechanisms that support the cell cycle.

MicroRNA-139-5p suppresses myosin heavy chain I and IIa expression via inhibition of the calcineurin/NFAT signaling pathway.

MicroRNAs (miRNAs) are a class of small non-coding RNAs that are widely involved in a variety of biological processes. Different skeletal muscle fiber type composition exhibits characteristic differences in functional properties and energy metabolism of skeletal muscle. However, the molecular mechanism by which miRNAs control the different type of muscle fiber formation is still not fully understood. In the present study, we characterized the role of microRNA-139-5p (miR-139-5p) in the regulation of myosin heavy chain (MyHC) isoform expression and its underlying mechanisms. Here we found that the expression of miR-139-5p was significantly higher in mouse slow-twitch muscle than in fast-twitch muscle. Overexpression of miR-139-5p downregulated the expression of MyHC I and MyHC IIa, whereas inhibition of miR-139-5p upregulated them. We also found that the levels of calcineurin (CaN), NFATc1, MEF2C and MCIP1.4, which are the components of CaN/NFAT signaling pathway that has shown to positively regulate slow fiber-selective gene expression, were notably inhibited by miR-139-5p overexpression. Furthermore, treatment of phenylephrine (PE), a α1-adrenoceptor agonist, abolished the inhibitory effect of miR-139-5p on MyHC I and MyHC IIa expression. Together, our findings indicated that the role of miR-139-5p in regulating the MyHC isoforms, especially MyHC I and MyHC IIa, may be achieved through inhibiting CaN/NFAT signaling pathway.

Importance of Full-Collapse Vesicle Exocytosis for Synaptic Fatigue-Resistance at Rat Fast and Slow Muscle Neuromuscular Junctions.

Neurotransmitter release during trains of activity usually involves two vesicle pools (readily releasable pool, or RRP, and reserve pool, or RP) and two exocytosis mechanisms ("full-collapse" and "kiss-and-run"). However, synaptic terminals are adapted to differing patterns of use and the relationship of these factors to enabling terminals to adapt to differing transmitter release demands is not clear. We have therefore tested their contribution to a terminal's ability to maintain release, or synaptic fatiguability in motor terminals innervating fast-twitch (fatiguable), and postural slow-twitch (fatigue-resistant) muscles. We used electrophysiological recording of neurotransmission and fluorescent dye markers of vesicle recycling to compare the effects of kinase inhibitors of varying myosin light chain kinase (MLCK) selectivity (staurosporine, wortmannin, LY294002 & ML-9) on vesicle pools, exocytosis mechanisms, and sustained neurotransmitter release, using postural-type activity train (20 Hz for 10 min) in these muscles. In both muscles, a small, rapidly depleted vesicle pool (the RRP) was inhibitor insensitive, continuing to release FM1-43, which is a marker of full-collapse exocytosis. MLCK-inhibiting kinases blocked all remaining FM1-43 loss from labelled vesicles. However, FM2-10 release only slowed, indicating continuing kiss-and-run exocytosis. Despite this, kinase inhibitors did not affect transmitter release fatiguability under normal conditions. However, augmenting release in high Ca2+ entirely blocked the synaptic fatigue-resistance of terminals in slow-twitch muscles. Thus, full-collapse exocytosis from most vesicles (the RP) is not essential for maintaining release during a single prolonged train. However, it becomes critical in fatigue-resistant terminals during high vesicle demand.

Uncovering the embryonic development-related proteome and metabolome signatures in breast muscle and intramuscular fat of fast-and slow-growing chickens.

BACKGROUND: Skeletal muscle development is closely linked to meat production and its quality. This study is the first to quantify the proteomes and metabolomes of breast muscle in two distinct chicken breeds at embryonic day 12 (ED 12), ED 17, post-hatch D 1 and D 14 using mass spectrometry-based approaches. RESULTS: Results found that intramuscular fat (IMF) accumulation increased from ED 17 to D 1 and that was exactly the opposite of when most obvious growth of muscle occurred (ED 12 - ED 17 and D 1 - D 14). For slow-growing Beijing-You chickens, Ingenuity Pathway Analysis of 77-99 differential abundance (DA) proteins and 63-72 metabolites, indicated significant enrichment of molecules and pathways related to protein processing and PPAR signaling. For fast-growing Cobb chickens, analysis of 68-95 DA proteins and 56-59 metabolites demonstrated that molecules and pathways related to ATP production were significantly enriched after ED12. For IMF, several rate-limiting enzymes for beta-oxidation of fatty acid (ACADL, ACAD9, HADHA and HADHB) were identified as candidate biomarkers for IMF deposition in both breeds. CONCLUSIONS: This study found that ED 17 - D 1 was the earliest period for IMF accumulation. Pathways related to protein processing and PPAR signaling were enriched to support high capacity of embryonic IMF accumulation in Beijing-You. Pathways related to ATP production were enriched to support the fast muscle growth in Cobb. The beta-oxidation of fatty acid is identified as the key pathway regulating chicken IMF deposition at early stages.

Identification of Small Molecules Which Induce Skeletal Muscle Differentiation in Embryonic Stem Cells via Activation of the Wnt and Inhibition of Smad2/3 and Sonic Hedgehog Pathways.

The multilineage differentiation capacity of mouse and human embryonic stem (ES) cells offers a testing platform for small molecules that mediate mammalian lineage determination and cellular specialization. Here we report the identification of two small molecules which drives mouse 129 ES cell differentiation to skeletal muscle with high efficiency without any genetic modification. Mouse embryoid bodies (EBs) were used to screen a library of 1,000 small molecules to identify compounds capable of inducing high levels of Pax3 mRNA. Stimulation of EBs with SMIs (skeletal muscle inducer, SMI1 and SMI2) from the screen resulted in a high percentage of intensively twitching skeletal muscle fibers 3 weeks after induction. Gene expression profiling studies that were carried out for mode of actions analysis showed that SMIs activated genes regulated by the Wnt pathway and inhibited expression of Smad2/3 and Sonic Hedgehog (Shh) target genes. A combination of three small molecules known to modulate these three pathways acted similarly to the SMIs found here, driving ES cells from 129 as well as Balb/c and C57Bl/6 to skeletal muscle. Taken together, these data demonstrate that the SMI drives ES cells to skeletal muscle via concerted activation of the Wnt pathway, and inhibition of Smad2/3 signaling and Shh pathways. This provides important developmental biological information about skeletal muscle differentiation from embryonic stem cells and may lead to the development of new therapeutics for muscle disease.

Changes in contractile and metabolic parameters of skeletal muscle as rats age from 3 to 12 months.

Laboratory rats are considered mature at 3 months despite that musculoskeletal growth is still occurring. Changes in muscle physiological and biochemical characteristics during development from 3 months, however, are not well understood. Whole muscles and single skinned fibres from fast-twitch extensor digitorum longus (EDL) and predominantly slow-twitch soleus (SOL) muscles were examined from male Sprague-Dawley rats (3, 6, 9, 12 months). Ca2+ sensitivity of contractile apparatus decreased with age in both fast- (~ 0.04 pCa units) and slow-twitch (~ 0.07 pCa units) muscle fibres, and specific force increased (by ~ 50% and ~ 25%, respectively). Myosin heavy chain composition of EDL and SOL muscles altered to a small extent with age (decrease in MHCIIa proportion after 3 months). Glycogen content increased with age (~ 80% in EDL and 25% in SOL) and GLUT4 protein density decreased (~ 35 and 20%, respectively), whereas the glycogen-related enzymes were little changed. GAPDH protein content was relatively constant in both muscle types, but COXIV protein decreased ~ 40% in SOL muscle. Calsequestrin (CSQ) and SERCA densities remained relatively constant with age, whereas there was a progressive ~ 2-3 fold increase in CSQ-like proteins, though their role and importance remain unclear. There was also ~ 40% decrease in the density of the Na+, K+-ATPase (NKA) α1 subunit in EDL and the α2 subunit in SOL. These findings emphasise there are substantial changes in skeletal muscle function and the density of key proteins during early to mid-adulthood in rats, which need to be considered in the design and interpretation of experiments.

Transdifferentiation of fast skeletal muscle into functional endothelium in vivo by transcription factor Etv2.

Etsrp/Etv2 (Etv2) is an evolutionarily conserved master regulator of vascular development in vertebrates. Etv2 deficiency prevents the proper specification of the endothelial cell lineage, while its overexpression causes expansion of the endothelial cell lineage in the early embryo or in embryonic stem cells. We hypothesized that Etv2 alone is capable of transdifferentiating later somatic cells into endothelial cells. Using heat shock inducible Etv2 transgenic zebrafish, we demonstrate that Etv2 expression alone is sufficient to transdifferentiate fast skeletal muscle cells into functional blood vessels. Following heat treatment, fast skeletal muscle cells turn on vascular genes and repress muscle genes. Time-lapse imaging clearly shows that muscle cells turn on vascular gene expression, undergo dramatic morphological changes, and integrate into the existing vascular network. Lineage tracing and immunostaining confirm that fast skeletal muscle cells are the source of these newly generated vessels. Microangiography and observed blood flow demonstrated that this new vasculature is capable of supporting circulation. Using pharmacological, transgenic, and morpholino approaches, we further establish that the canonical Wnt pathway is important for induction of the transdifferentiation process, whereas the VEGF pathway provides a maturation signal for the endothelial fate. Additionally, overexpression of Etv2 in mammalian myoblast cells, but not in other cell types examined, induced expression of vascular genes. We have demonstrated in zebrafish that expression of Etv2 alone is sufficient to transdifferentiate fast skeletal muscle into functional endothelial cells in vivo. Given the evolutionarily conserved function of this transcription factor and the responsiveness of mammalian myoblasts to Etv2, it is likely that mammalian muscle cells will respond similarly.

Role of Muscle Morphology in Jumping, Sprinting, and Throwing Performance in Participants With Different Power Training Duration Experience.

The aim of the study was to examine the correlation between muscle morphology and jumping, sprinting, and throwing performance in participants with different power training duration experience. Thirty-six power-trained young men were assigned to 3 groups according to the length of their power training: less experienced (<1 year), moderately experienced (1-3 years), and experienced (4-7 years). All participants performed countermovement and squat jumps, 60-m sprint, and shot throws twice. Lean body mass (LBM) was evaluated with dual-energy x-ray absorptiometry and thigh muscle cross-sectional area (CSA) with anthropometry. The vastus lateralis architecture and fiber type composition were evaluated with ultrasonography and muscle biopsies, respectively. When all subjects were considered as 1 group (n = 36), jumping performance was correlated with LBM, fascicle length, and type II fiber CSA; sprinting performance was correlated with estimated thigh muscle CSA alone; and shot throwing was correlated with LBM and type I, IIA fiber CSA. In the least experienced group, the LBM of the lower extremities was the most significant contributor for power performance, whereas in the moderately experienced group, the LBM, architectural properties, and type II fiber percentage CSA were the most significant contributors. For the experienced group, fascicle length and type II fiber percentage CSA were the most significant factors for power performance. These data suggest that jumping performance is linked with muscle morphology, regardless of strength or power training. The vastus lateralis muscle morphology could only partially explain throwing performance, whereas it cannot predict sprinting performance. Power performance in experienced participants rely more on the quality of the muscle tissue rather than the quantity.

Fiber type-specific response of skeletal muscle satellite cells to high-intensity resistance training in dialysis patients.

INTRODUCTION: The aim of this study was to assess the effect of high-intensity resistance training on satellite cell (SC) and myonuclear number in the muscle of patients undergoing dialysis. METHODS: Patients (n = 21) underwent a 16-week control period, followed by 16 weeks of resistance training 3 times weekly. SC and myonuclear number were determined by immunohistochemistry of vastus lateralis muscle biopsy cross-sections. Knee extension torque was tested in a dynamometer. RESULTS: During training, SCs/type I fibers increased by 15%, whereas SCs/type II fibers remained unchanged. Myonuclear content of type II, but not type I, fibers increased with training. Before the control period, the SC content of type II fibers was lower than that of type I fibers, whereas contents were comparable when normalized to fiber area. Torque increased after training. CONCLUSIONS: Increased myonuclear content of type II muscle fibers of dialysis patients who perform resistance training suggests that SC dysfunction is not the limiting factor for muscle growth.

Fiber types of the anterior and lateral cervical muscles in elderly males.

PURPOSE: The anterior and lateral cervical muscles (ALCM) are generally considered to be postural, yet few studies have investigated ALCM fiber types to help clarify the function of these muscles. This study aimed to systematically investigate ALCM fiber types in cadavers. METHODS: Anterior and lateral cervical muscles (four scalenus anterior, medius, posterior muscles; five longus colli, five longus capitis taken bilaterally from one cadaver) were removed from four male embalmed cadavers (mean age 87.25 years). Paraffin-embedded specimens were sectioned then stained immunohistochemically to identify type I and II skeletal muscle fibers. Proportional fiber type numbers and cross-sectional area (CSA) occupied by fiber types were determined using stereology (random systematic sampling). Results were analyzed using ANOVA (P < 0.05) and descriptive statistics. RESULTS: Scalenus anterior had the greatest average number and CSA of type I fibers (71.9 and 83.7%, respectively); longus capitis had the lowest number (48.5%) and CSA (61.4%). All scalene muscles had significantly greater type I CSA than longus capitis and longus colli; scalenus anterior and medius had significantly greater type I numbers than longus capitis and longus colli. Some significant differences were observed between individual cadavers in longus colli for CSA, and longus capitis for number. CONCLUSION: The ALCM do not share a common functional fiber type distribution, although similar fiber type distributions are shared by longus colli and longus capitis, and by the scalene muscles. Contrary to conventional descriptions, longus colli and longus capitis have type I fiber proportions indicative of postural as well as phasic muscle function.

Comparative analysis of rat mesenchymal stem cells derived from slow and fast skeletal muscle in vitro.

PURPOSE: Skeletal muscle comprises different kinds of muscle fibres that can be classified as slow and fast fibres. The purpose of this study was to compare the yield, proliferation, and multi-potentiality of rat mesenchymal stem cells (MSCs) from the tibialis anterior (TA; fast muscle) and soleus (SO; slow muscle) in vitro. METHODS: The TA and SO muscles were harvested, and isolated cells were plated. After two hours, the cells were washed extensively to remove any cell that did not adhere to the cell culture plate. The adherent cells, namely MSCs, were then cultured. Both types of MSCs were differentiated toward the osteogenic, chondrogenic and adipogenic lineages using lineage specific induction factors. RESULTS: The colony-forming unit fibroblast (CFU-F) assay revealed that the SO contained significantly higher quantities of MSCs than the TA. The self-renewal capacity of MSCs derived from the TA was significantly higher at later passages (passage 9-11). Both types of MSCs exhibited similar cell surface antigens to bone marrow (BM)-derived MSCs and were positive for CD29, CD44, and CD90 and negative for CD11b, CD34, and CD45. TA-derived MSCs were superior in terms of osteogenic differentiation capacity, but there was no significant difference in chondrogenic and adipogenic differentiation capacity. CONCLUSION: Our results demonstrated significant differences in the properties of muscle-derived MSCs from different muscle types (i.e. fast or slow muscles). The greater expandability and osteogenic differentiation ability of TA-derived MSCs suggests that fast muscle may be a better source for generating large numbers of MSCs for bone regeneration.