Number Of Myonuclei Research Articles

Massage Induces an Increase in DNA Synthesis and Satellite Cell Number in Rat Muscle Recovering from Atrophy

BackgroundMassage of skeletal muscle is associated with many benefits, but very few mechanisms are currently identified. Massage in the form of cyclic compressive loading (CCL) results in an immunomodulatory effect on injured and uninjured muscles, but its effect on muscle size is unclear. We have recently shown that muscle fiber cross sectional area and protein synthesis were elevated in response to CCL in rats that were recovering from atrophy. Surprisingly, it was also found that DNA synthesis was elevated with CCL in muscles undergoing regrowth after disuse. It is currently unknown which cell type in muscle would be undergoing DNA replication in response to massage, but we recently found that satellite cells are elevated after one bout of CCL in unperturbed rats. Therefore, the goal of this investigation was to identify which cells were increased in number to account for the observed elevation in DNA synthesis; we hypothesize that satellite cell number is greater in the massaged limb.MethodsMale Fisher 344‐BN rats (10 months) were divided into 4 groups (n=8): weight bearing (WB), hindlimb suspended for 14 days (HS), HS and reloaded for 7 days (RE), and RE with 4 bouts of massage applied every other day during the reloading period (REM) starting the first bout at the moment of reloading; right gastrocnemius muscles were subjected to CCL. Muscles were collected and frozen 24 hours after the last bout of CCL. Muscle sections were cut and immunohistochemistry was performed to identify myonuclei (dystrophin and DAPI), M2 macrophages (ED2+), satellite cells (Pax7+), endothelial cells (Lectin+), and fibroblasts (TCF4+). Cell types and myonuclei were visualized using Axiovision image analysis software (Zeiss) and expressed per fiber number.ResultsNo significant differences were observed for ED2, TCF4, or lectin positive cells with HS, RE, or with massage during RE, indicating that these cells types had not changed in number and likely did not explain the increase in DNA synthesis with massage. Satellite cell number (Pax7+) was significantly decreased with HS, was restored with reloading, and was significantly elevated with massage compared to weight bearing and reloading, suggesting that this cell type was responsible for the observed DNA synthesis. However, the number of myonuclei and centrally located nuclei was not changed under any condition.ConclusionResults indicate that the observed increase in DNA synthesis with massage during muscle regrowth after atrophy could be explained by satellite cell proliferation. Since no increase in myonuclear count was found, we suggest that these satellite cells likely do not contribute to new myonuclei, but rather could be involved in the modulation of the extracellular matrix.Support or Funding InformationThis research was funded by NIH grant AG042699. Amanda Hayek received funding from the STRIDE Undergraduate Summer Research Fellowship supported by the American Physiological Society and NHLBI, 1 R25 HL115473‐01.

Synergist Ablation as a Rodent Model to Study Satellite Cell Dynamics in Adult Skeletal Muscle.

In adult skeletal muscles, satellite cells are the primary myogenic stem cells involved in myogenesis. Normally, they remain in a quiescent state until activated by a stimulus, after which they proliferate, differentiate, and fuse into an existing myofiber or form a de novo myofiber. To study satellite cell dynamics in adult murine models, most studies utilize regeneration models in which the muscle is severely damaged and requires the participation from satellite cells in order to repair. Here, we describe a model to study satellite cell behavior in muscle hypertrophy that is independent of muscle regeneration.Synergist ablation surgery involves the surgical removal of the gastrocnemius and soleus muscles resulting in functional overload of the remaining plantaris muscle. This functional overload results in myofiber hypertrophy, as well as the activation, proliferation, and fusion of satellite cells into the myofibers. Within 2 weeks of functional overload, satellite cell content increases approximately 275 %, an increase that is accompanied with a ~60 % increase in the number of myonuclei. Therefore, this can be used as an alternative model to study satellite cell behavior in adulthood that is different from regeneration, and capable of revealing new satellite cell functions in regulating muscle adaptation.

Muscle memory and a new cellular model for muscle atrophy and hypertrophy.

Memory is a process in which information is encoded, stored, and retrieved. For vertebrates, the modern view has been that it occurs only in the brain. This review describes a cellular memory in skeletal muscle in which hypertrophy is 'remembered' such that a fibre that has previously been large, but subsequently lost its mass, can regain mass faster than naive fibres. A new cell biological model based on the literature, with the most reliable methods for identifying myonuclei, can explain this phenomenon. According to this model, previously untrained fibres recruit myonuclei from activated satellite cells before hypertrophic growth. Even if subsequently subjected to grave atrophy, the higher number of myonuclei is retained, and the myonuclei seem to be protected against the elevated apoptotic activity observed in atrophying muscle tissue. Fibres that have acquired a higher number of myonuclei grow faster when subjected to overload exercise, thus the nuclei represent a functionally important 'memory' of previous strength. This memory might be very long lasting in humans, as myonuclei are stable for at least 15 years and might even be permanent. However, myonuclei are harder to recruit in the elderly, and if the long-lasting muscle memory also exists in humans, one should consider early strength training as a public health advice. In addition, myonuclei are recruited during steroid use and encode a muscle memory, at least in rodents. Thus, extending the exclusion time for doping offenders should be considered.

Pervasive satellite cell contribution to uninjured adult muscle fibers.

BackgroundAdult skeletal muscle adapts to functional needs, maintaining consistent numbers of myonuclei and stem cells. Although resident muscle stem cells or satellite cells are required for muscle growth and repair, in uninjured muscle, these cells appear quiescent and metabolically inactive. To investigate the satellite cell contribution to myofibers in adult uninjured skeletal muscle, we labeled satellite cells by inducing a recombination of LSL-tdTomato in Pax7CreER mice and scoring tdTomato+ myofibers as an indicator of satellite cell fusion.ResultsSatellite cell fusion into myofibers plateaus postnatally between 8 and 12 weeks of age, reaching a steady state in hindlimb muscles, but in extra ocular or diaphragm muscles, satellite cell fusion is maintained at postnatal levels irrespective of the age assayed. Upon recombination and following a 2-week chase in 6-month-old mice, tdTomato-labeled satellite cells fused into myofibers as 20, 50, and 80 % of hindlimb, extra ocular, and diaphragm myofibers, respectively, were tdTomato+. Satellite cells contribute to uninjured myofibers either following a cell division or directly without an intervening cell division.ConclusionsThe frequency of satellite cell fusion into the skeletal muscle fibers is greater than previously estimated, suggesting an important functional role for satellite cell fusion into adult myofibers and a requirement for active maintenance of satellite cell numbers in uninjured skeletal muscle.

Effects of strength training on muscle cellular outcomes in prostate cancer patients on androgen deprivation therapy.

Androgen deprivation therapy (ADT) improves life expectancy in prostate cancer (PCa) patients, but is associated with adverse effects on muscle mass. Here, we investigated the effects of strength training during ADT on muscle fiber cross-sectional area (CSA) and regulators of muscle mass. PCa patients on ADT were randomized to 16 weeks of strength training (STG) (n = 12) or a control group (CG; n = 11). Muscle biopsies were obtained from m. vastus lateralis and analyzed by immunohistochemistry and western blot. Muscle fiber CSA increased with strength training (898 μm(2) , P = 0.04), with the only significant increase observed in type II fibers (1076 μm(2) , P = 0.03). There was a trend toward a difference in mean change between groups myonuclei number (0.33 nuclei/fiber, P = 0.06), with the only significant increase observed in type I fibers, which decreased the myonuclear domain size of type I fibers (P = 0.05). Satellite cell numbers and the content of androgen receptor and myostatin remained unchanged. Sixteen weeks of strength training during ADT increased type II fiber CSA and reduced myonuclear domain in type I fibers in PCa patients. The increased number of satellite cells normally seen following strength training was not observed.

Post-exercise cold water immersion attenuates acute anabolic signalling and long-term adaptations in muscle to strength training.

We investigated functional, morphological and molecular adaptations to strength training exercise and cold water immersion (CWI) through two separate studies. In one study, 21 physically active men strength trained for 12 weeks (2 days per week), with either 10 min of CWI or active recovery (ACT) after each training session. Strength and muscle mass increased more in the ACT group than in the CWI group (P < 0.05). Isokinetic work (19%), type II muscle fibre cross-sectional area (17%) and the number of myonuclei per fibre (26%) increased in the ACT group (all P < 0.05), but not the CWI group. In another study, nine active men performed a bout of single-leg strength exercises on separate days, followed by CWI or ACT. Muscle biopsies were collected before and 2, 24 and 48 h after exercise. The number of satellite cells expressing neural cell adhesion molecule (NCAM) (10-30%) and paired box protein (Pax7) (20-50%) increased 24-48 h after exercise with ACT. The number of NCAM(+) satellite cells increased 48 h after exercise with CWI. NCAM(+) - and Pax7(+) -positive satellite cell numbers were greater after ACT than after CWI (P < 0.05). Phosphorylation of p70S6 kinase(Thr421/Ser424) increased after exercise in both conditions but was greater after ACT (P < 0.05). These data suggest that CWI attenuates the acute changes in satellite cell numbers and activity of kinases that regulate muscle hypertrophy, which may translate to smaller long-term training gains in muscle strength and hypertrophy. The use of CWI as a regular post-exercise recovery strategy should be reconsidered.

Hypothyroidism modifies morphometry and thyroid-hormone receptor expression in periurethral muscles of female rabbits.

To evaluate the morphometry and thyroid-hormone receptor (TR) expression in pelvic (pubococcygeus, Pcm) and perineal (bulbospongiosus, Bsm) muscles of control and hypothyroid female rabbits. Hypothyroidism was induced administering 0.02% methimazole in the drinking water for one month. Hematoxylin-eosin stained muscle sections were used to evaluate the fiber cross-sectional area (CSA) and the number of peripheral myonuclei per fiber. Immunohistochemistry was used to calculate the proportion of TR immunoreactive nuclei per fiber. Significant differences were considered at a P ≤ 0.05. As compared to control rabbits, hypothyroidism increased the averaged fiber CSA and the myonuclei per fiber in the Bsm. Although the myonuclei number per fiber was also increased in the Pcm, the effect concerning the fiber CSA was only observed in a fraction of the Pcm fibers. Both TRα and TRβ were similarly expressed in the Pcm and Bsm. Hypothyroidism increased the expression of the TRα in the Bsm. Meanwhile, the expression of TR isoforms in the Pcm was not altered. Our findings support that the TR signaling is directly involved in morphometrical changes induced by hypothyroidism in the Pcm and Bsm. The effect of hypothyroidism on the Pcm and Bsm could be related to the different type of fiber and metabolism that these muscles have. Neurourol. Urodynam. 35:895-901, 2016. © 2015 Wiley Periodicals, Inc.

Cellular Mechanism of Muscle Memory

It is evident that previously trained muscles reacquire strength and volume at an accelerated rate when re-subjected to resistance training (REXT) even after prolonged detraining. However, specific cellular mechanisms of this phenomenon known as “muscle memory” remain elusive. Because acquired myonuclei have been shown as important biological mediators, and because regulatory genes that control mitochondrial biogenesis are encoded in nuclear genome, we hypothesized, here, that the increased number of nuclei within myofibers would facilitate mitochondrial remodeling and muscle hypertrophy in previously trained muscles during retraining. PURPOSE: To identify a cellular memory mechanism retained in pre-trained muscles and to investigate its effects on structural, functional, and mitochondrial adaptations to retraining preceded by a long-term detraining period. METHODS: Thirty-two SD rats were randomly assigned to 4 groups (n=8 each): Control (C), Pre-training (PT), Training (T), and Retraining (RT). REXT was performed at age of either 8-wk (REXT1) or 36-wk old (REXT2), and were carried out by ladder climbing (1 meter in height) with weights attached to the tail. Each training session consisted of 3 sets of 5 climbing repetitions. Animals were subjected to 2 sessions/day, every third day for 8 wk. The PT and T group performed either REXT1 or REXT2, respectively, where the RT group performed both REXTs 1 and 2. Immunohistochemistry, H&E, COX and SDH staining, and western blot were performed. Comparisons were made using one-way ANOVA followed by a LSD post-hoc test. RESULTS: Body weight was higher in C and PT group compared to T and RT group. DAPI-Pax7 co-staining revealed that myonuclei number was higher (~13%) in PT and RT group compared to C group. Muscle cross-sectional area and muscle weight were greater in RT group compared to T group (p<0.01 for both). COX and SDH activities were significantly greater in RT group compared to T group. PGC-1α protein expression level was greater in RT compared to T group. The expression levels of mitochondrial fusion/fission proteins (i.e. Mfn2, Fis1 and Drp1) were higher in RT group compared to T group (p<0.05). CONCLUSION: Data indicate the acquired myonuclei within a pre-trained muscle fiber as intracellular mediators for the facilitated muscular and mitochondrial adaptations.

The effect of an ActRIIB ligand trapping agent on the number of satellite cells and myonuclei in dystrophic (mdx) muscle fibers

Duchenne muscular dystrophy is characterized by repeated cycles of degeneration and regeneration ultimately leading to respiratory failure and death. Muscle growth is largely under the control of myostatin, which negatively influences fiber growth and regeneration by binding to the ActRIIB receptor. Ligand trapping agents for the ActRIIB receptor (RAP‐435) are therefore currently being tested as therapeutic agents using the mdx mouse model for Duchenne muscular dystrophy. The present study utilized confocal immunochemical techniques to examine the effects of in vivo RAP‐435 treatment on the number of satellite cells and myonuclei associated with isolated mdx costal diaphragm fibers. One month old mdx mice were treated with RAP435 or vehicle for one month. Following treatment, the isolated muscles were exposed to 0.2% collagenase. Satellite cells were identified with a PAX 7 primary and an AlexaFluor 488 secondary antibody. Myonuclei were identified by DAPI. Mdx costal diaphragm fibers exhibited approximately 700 myonuclei and 5 satellite cells per muscle fiber. Experiments comparing specific age‐matched nondystrophic and mdx respiratory muscles will determine if the regeneration characteristic of dystrophic muscle is associated with corresponding increases in the number of myonuclei per fiber. RAP‐435 treatment influenced neither the number of myonuclei nor satellite cells per muscle fiber. Morphometric analyses are being performed in conjunction with these confocal studies to determine if ActRIIB inhibition specifically influences myonuclear domain in promoting fiber growth and regeneration.

Mixed lactate and caffeine compound increases satellite cell activity and anabolic signals for muscle hypertrophy.

We examined whether a mixed lactate and caffeine compound (LC) could effectively elicit proliferation and differentiation of satellite cells or activate anabolic signals in skeletal muscles. We cultured C2C12 cells with either lactate or LC for 6 h. We found that lactate significantly increased myogenin and follistatin protein levels and phosphorylation of P70S6K while decreasing the levels of myostatin relative to the control. LC significantly increased protein levels of Pax7, MyoD, and Ki67 in addition to myogenin, relative to control. LC also significantly increased follistatin expression relative to control and stimulated phosphorylation of mTOR and P70S6K. In an in vivo study, male F344/DuCrlCrlj rats were assigned to control (Sed, n = 10), exercise (Ex, n = 12), and LC supplementation (LCEx, n = 13) groups. LC was orally administered daily. The LCEx and Ex groups were exercised on a treadmill, running for 30 min at low intensity every other day for 4 wk. The LCEx group experienced a significant increase in the mass of the gastrocnemius (GA) and tibialis anterior (TA) relative to both the Sed and Ex groups. Furthermore, the LCEx group showed a significant increase in the total DNA content of TA compared with the Sed group. The LCEx group experienced a significant increase in myogenin and follistatin expression of GA relative to the Ex group. These results suggest that administration of LC can effectively increase muscle mass concomitant with elevated numbers of myonuclei, even with low-intensity exercise training, via activated satellite cells and anabolic signals.

Doublecortin marks a new population of transiently amplifying muscle progenitor cells and is required for myofiber maturation during skeletal muscle regeneration.

Muscle satellite cells are indispensable for muscle regeneration, but the functional diversity of their daughter cells is unknown. Here, we show that many Pax7(+)MyoD(-) cells locate both beneath and outside the basal lamina during myofiber maturation. A large majority of these Pax7(+)MyoD(-) cells are not self-renewed satellite cells, but have different potentials for both proliferation and differentiation from Pax7(+)MyoD(+) myoblasts (classical daughter cells), and are specifically marked by expression of the doublecortin (Dcx) gene. Transplantation and lineage-tracing experiments demonstrated that Dcx-expressing cells originate from quiescent satellite cells and that the microenvironment induces Dcx in myoblasts. Expression of Dcx seems to be necessary for myofiber maturation because Dcx-deficient mice exhibited impaired myofiber maturation resulting from a decrease in the number of myonuclei. Furthermore, in vitro and in vivo studies suggest that one function of Dcx in myogenic cells is acceleration of cell motility. These results indicate that Dcx is a new marker for the Pax7(+)MyoD(-) subpopulation, which contributes to myofiber maturation during muscle regeneration.

Deficient nitric oxide signalling impairs skeletal muscle growth and performance: involvement of mitochondrial dysregulation.

BackgroundNitric oxide (NO), generated in skeletal muscle mostly by the neuronal NO synthases (nNOSμ), has profound effects on both mitochondrial bioenergetics and muscle development and function. The importance of NO for muscle repair emerges from the observation that nNOS signalling is defective in many genetically diverse skeletal muscle diseases in which muscle repair is dysregulated. How the effects of NO/nNOSμ on mitochondria impact on muscle function, however, has not been investigated yet.MethodsIn this study we have examined the relationship between the NO system, mitochondrial structure/activity and skeletal muscle phenotype/growth/functions using a mouse model in which nNOSμ is absent. Also, NO-induced effects and the NO pathway were dissected in myogenic precursor cells.ResultsWe show that nNOSμ deficiency in mouse skeletal muscle leads to altered mitochondrial bioenergetics and network remodelling, and increased mitochondrial unfolded protein response (UPRmt) and autophagy. The absence of nNOSμ is also accompanied by an altered mitochondrial homeostasis in myogenic precursor cells with a decrease in the number of myonuclei per fibre and impaired muscle development at early stages of perinatal growth. No alterations were observed, however, in the overall resting muscle structure, apart from a reduced specific muscle mass and cross sectional areas of the myofibres. Investigating the molecular mechanisms we found that nNOSμ deficiency was associated with an inhibition of the Akt-mammalian target of rapamycin pathway. Concomitantly, the Akt-FoxO3-mitochondrial E3 ubiquitin protein ligase 1 (Mul-1) axis was also dysregulated. In particular, inhibition of nNOS/NO/cyclic guanosine monophosphate (cGMP)/cGMP-dependent-protein kinases induced the transcriptional activity of FoxO3 and increased Mul-1 expression. nNOSμ deficiency was also accompanied by functional changes in muscle with reduced muscle force, decreased resistance to fatigue and increased degeneration/damage post-exercise.ConclusionsOur results indicate that nNOSμ/NO is required to regulate key homeostatic mechanisms in skeletal muscle, namely mitochondrial bioenergetics and network remodelling, UPRmt and autophagy. These events are likely associated with nNOSμ-dependent impairments of muscle fibre growth resulting in a deficit of muscle performance.Electronic supplementary materialThe online version of this article (doi:10.1186/s13395-014-0022-6) contains supplementary material, which is available to authorized users.

Stand-up exercise training facilitates muscle recovery from disuse atrophy by stimulating myogenic satellite cell proliferation in mice.

Determining the cellular and molecular recovery processes in inactivity – or unloading –induced atrophied muscles should improve rehabilitation strategies. We assessed the effects of stand‐up exercise (SE) training on the recovery of atrophied skeletal muscles in male mice. Mice were trained to stand up and press an elevated lever in response to a light‐tone cue preceding an electric foot shock and then subjected to tail suspension (TS) for 2 weeks to induce disuse atrophy in hind limb muscles. After release from TS, mice were divided into SE‐trained (SE cues: 25 times per set, two sets per day) and non‐SE‐trained groups. Seven days after the training, average myofiber cross‐sectional area (CSA) of the soleus muscle was significantly greater in the SE‐trained group than in the non‐SE‐trained group (1843 ± 194 μm2 vs. 1315 ± 153 μm2). Mean soleus muscle CSA in the SE trained group was not different from that in the CON group subjected to neither TS nor SE training (2005 ± 196 μm2), indicating that SE training caused nearly complete recovery from muscle atrophy. The number of myonuclei per myofiber was increased by ~60% in the SE‐trained group compared with the non‐SE‐trained and CON groups (0.92 ± 0.03 vs. 0.57 ± 0.03 and 0.56 ± 0.11, respectively). The number of proliferating myonuclei, identified by 5‐ethynyl‐2′‐deoxyuridine staining, increased within the first few days of SE training. Thus, it is highly likely that myogenic satellite cells proliferated rapidly in atrophied muscles in response to SE training and fused with existing myofibers to reestablish muscle mass.

Nutraceutical properties of chestnut flours: beneficial effects on skeletal muscle atrophy.

Plants contain a wide range of non-nutritive phytochemicals, many of which have protective or preventive properties for human diseases. The aim of the present work has been to investigate the nutraceutical properties of sweet chestnut flour extracts obtained from fruits collected from 7 geographic areas of Tuscany (Italy), and their ability in modulating skeletal muscle atrophy. We found that the cultivars from different geographic areas are characterized by the composition and quantity of various nutrients and specific bioactive components, such as tocopherols, polyphenols and sphingolipids. The nutraceutical properties of chestnut sweet flours have been evaluated in C2C12 myotubes induced to atrophy by serum deprivation or dexamethasone. We found that the pretreatment with both total extracts of tocopherols and sphingolipids is able to counterbalance cell atrophy, reducing the decrease in myotube size and myonuclei number, and attenuating protein degradation and the increase in expression of MAFbx/atrogin-1 (a muscle-specific atrophy marker). By contrast, polyphenol extracts were not able to prevent atrophy. Since we also found that γ-tocopherol is the major form of tocopherol in sweet flour and its content differs depending on the procedure of sweet flour preparation, the mechanisms by which γ-tocopherol as well as sphingolipids affect skeletal muscle cell atrophy have been also investigated. This is the first evidence that chestnut sweet flour is a natural source of specific bioactive components with a relevant role in the prevention of cell degeneration and maintenance of skeletal muscle mass, opening important implications in designing appropriate nutritional therapeutic approaches to skeletal muscle atrophy.

Muscle nuclei remember to cheat death

Muscle nuclei remember to cheat death

A cellular memory mechanism aids overload hypertrophy in muscle long after an episodic exposure to anabolic steroids

Previous strength training with or without the use of anabolic steroids facilitates subsequent re-acquisition of muscle mass even after long intervening periods of inactivity. Based on in vivo and ex vivo microscopy we here propose a cellular memory mechanism residing in the muscle cells. Female mice were treated with testosterone propionate for 14 days, inducing a 66% increase in the number of myonuclei and a 77% increase in fibre cross-sectional area. Three weeks after removing the drug, fibre size was decreased to the same level as in sham treated animals, but the number of nuclei remained elevated for at least 3 months (>10% of the mouse lifespan). At this time, when the myonuclei-rich muscles were exposed to overload-exercise for 6 days, the fibre cross-sectional area increased by 31% while control muscles did not grow significantly. We suggest that the lasting, elevated number of myonuclei constitutes a cellular memory facilitating subsequent muscle overload hypertrophy. Our findings might have consequences for the exclusion time of doping offenders. Since the ability to generate new myonuclei is impaired in the elderly our data also invites speculation that it might be beneficial to perform strength training when young in order to benefit in senescence.

Predicted high-performing piglets exhibit more and larger skeletal muscle fibers1

Postnatal (muscle) growth potential in pigs depends on the total number and hypertrophy of myofibers in skeletal muscle tissue. In a previous study an algorithm was developed to predict piglet BW at the end of the nursery period (10 wk of age) on the basis of BW at birth, at weaning, and at 6 wk of age. The objective of this study was to determine whether the differences in growth performance between poor (PP) and high (HP) performing piglets could be the result of different skeletal muscle properties. Therefore, from a total of 368 piglets (offspring from Hypor sows bred to TOPIGS sires) 2 groups with a divergent growth performance were selected at 6 wk of age: HP (n = 20, predicted BW at 10 wk of age 26.8-30.9 kg) and PP (n = 20, predicted BW at 10 wk of age 16.0-22.9 kg). Piglets were euthanized at 10 wk of age, and samples of the semitendinosus muscle (STN) were collected for histochemistry and gene expression analysis using quantitative PCR (qPCR). At 10 wk of age, realized BW did not differ from predicted BW in either group (P > 0.880). The HP piglets exhibited greater ADG and ADFI from 6 to 10 wk and greater BW at birth and 6 and 10 wk of age (P ≤ 0.002) compared with the PP piglets, whereas G:F ratio was similar (P = 0.417). Superior growth performance of HP piglets was associated with a 1.27-fold higher IGF1 plasma concentration at 10 wk compared with the PP piglets (P = 0.044). The greater weight and muscle cross-sectional area of STN in HP piglets was due to a 1.20-fold increase in total muscle fiber number (TFN; P = 0.009) and 1.34-fold increase in fiber cross-sectional area (FCSA; P = 0.004) compared with the PP piglets. The number of myonuclei per red and intermediate fiber was greater in HP piglets (P ≤ 0.097), but the nucleus-to-cytoplasm ratio was unaffected by the performance group (P = 0.861). The mRNA expression of proliferating cell nuclear antigen (PCNA), paired box 7 (PAX7), myogenic factor 5 (MYF5), and myogenic differentiation factor (MYOD) did not differ between groups (P ≥ 0.327). However, IGF2-specific mRNA expression was numerically higher in the HP piglets (P = 0.101). The greater myofiber number, the higher degree of myofiber hypertrophy, and the increased muscular mRNA expression of IGF2 indicate that HP piglets exhibit a greater capacity for lean accretion and may grow faster until market weight. In summary, pigs that were selected for predicted high BW at 10 wk of age using a complex selection model had a superior muscularity in terms of greater TFN and FCSA, which may be of advantage for lean mass accretion in later life and for meat quality.

Effects of Recombinant Mechano-Dependent Growth Factor on the Background of Chronic Alcoholization in Rats

In alcoholised rats, proliferation of satellite cells consistently decreased as well as the number of myonuclei, while phosphorylation of p90RSK became reduced. The mechano-growth factor abministration increased the proliferate activity of the myogenic precursors and restored the myonuclei pool. Phosphorylation of p90RSK increased too.

Androgen-dependent impairment of myogenesis in spinal and bulbar muscular atrophy

Spinal and bulbar muscular atrophy (SBMA) is an inherited neuromuscular disease caused by expansion of a polyglutamine (polyQ) tract in the androgen receptor (AR). SBMA is triggered by the interaction between polyQ-AR and its natural ligands, testosterone and dihydrotestosterone (DHT). SBMA is characterized by the loss of lower motor neurons and skeletal muscle fasciculations, weakness, and atrophy. To test the hypothesis that the interaction between polyQ-AR and androgens exerts cell-autonomous toxicity in skeletal muscle, we characterized the process of myogenesis and polyQ-AR expression in DHT-treated satellite cells obtained from SBMA patients and age-matched healthy control subjects. Treatment with androgens increased the size and number of myonuclei in myotubes from control subjects, but not from SBMA patients. Myotubes from SBMA patients had a reduced number of nuclei, suggesting impaired myotube fusion and altered contractile structures. The lack of anabolic effects of androgens on myotubes from SBMA patients was not due to defects in myoblast proliferation, differentiation or apoptosis. DHT treatment of myotubes from SBMA patients increased nuclear accumulation of polyQ-AR and decreased the expression of interleukin-4 (IL-4) when compared to myotubes from control subjects. Following DHT treatment, exposure of myotubes from SBMA patients with IL-4 treatment rescued myonuclear number and size to control levels. This supports the hypothesis that androgens alter the fusion process in SBMA myogenesis. In conclusion, these results provide evidence of an androgen-dependent impairment of myogenesis in SBMA that could contribute to disease pathogenesis.

Mechanisms regulating skeletal muscle growth and atrophy

Skeletal muscle mass increases during postnatal development through a process of hypertrophy, i.e. enlargement of individual muscle fibers, and a similar process may be induced in adult skeletal muscle in response to contractile activity, such as strength exercise, and specific hormones, such as androgens and β-adrenergic agonists. Muscle hypertrophy occurs when the overall rates of protein synthesis exceed the rates of protein degradation. Two major signaling pathways control protein synthesis, the IGF1-Akt-mTOR pathway, acting as a positive regulator, and the myostatin-Smad2/3 pathway, acting as a negative regulator, and additional pathways have recently been identified. Proliferation and fusion of satellite cells, leading to an increase in the number of myonuclei, may also contribute to muscle growth during early but not late stages of postnatal development and in some forms of muscle hypertrophy in the adult. Muscle atrophy occurs when protein degradation rates exceed protein synthesis, and may be induced in adult skeletal muscle in a variety of conditions, including starvation, denervation, cancer cachexia, heart failure and aging. Two major protein degradation pathways, the proteasomal and the autophagic-lysosomal pathways, are activated during muscle atrophy and variably contribute to the loss of muscle mass. These pathways involve a variety of atrophy-related genes or atrogenes, which are controlled by specific transcription factors, such as FoxO3, which is negatively regulated by Akt, and NF-κB, which is activated by inflammatory cytokines.