Hindlimb suspension reduces muscle regeneration

Mozdziak, Paul; Truong, Quoc Van; Macius, Allison; Schultz, Edward

doi:10.1007/s004210050398

Cited by 38 publications

(37 citation statements)

References 17 publications

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“…identical changes occur in the muscles during unloading produced by caudal suspension in animals or prolonged bed rest in humans (Ferrando et al 1996, Bamman et al 1998, Mozdziak et al 1998, Wehling et al 2000. Muscle organ cultures sent in spaceflight also demonstrate atrophy in response to microgravity (Vandenburgh et al 1999).…”

Section: Introductionmentioning

confidence: 99%

Myostatin and insulin-like growth factor-I and -II expression in the muscle of rats exposed to the microgravity environment of the NeuroLab space shuttle flight

Lalani

Bhasin²,

Byhower³

et al. 2000

Journal of Endocrinology

156

115

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The mechanism of the loss of skeletal muscle mass that occurs during spaceflight is not well understood. Myostatin has been proposed as a negative modulator of muscle mass, and IGF-I and IGF-II are known positive regulators of muscle differentiation and growth. We investigated whether muscle loss associated with spaceflight is accompanied by increased levels of myostatin and a reduction in IGF-I and -II levels in the muscle, and whether these changes correlate with an increase in muscle proteolysis and apoptosis. Twelve male adult rats sent on the 17-day NASA STS-90 NeuroLab space flight were divided upon return to earth into two groups, and killed either 1 day later (R1) or after 13 days of acclimatization (R13). Ground-based control rats were maintained for the same periods in either vivarium (R3 and R15, respectively), or flight-simulated cages (R5 and R17, respectively). RNA and protein were isolated from the tibialis anterior, biceps femoris, quadriceps, and gastrocnemius muscles. Myostatin, IGF-I, IGF-II and proteasome 2c mRNA concentrations were determined by reverse transcription/PCR; myostatin and ubiquitin mRNA were also measured by Northern blot analysis; myostatin protein was estimated by immunohistochemistry; the apoptotic index and the release of 3-methylhistidine were determined respectively by the TUNEL assay and by HPLC. Muscle weights were 19-24% lower in the R1 rats compared with the control R3 and R5 rats, but were not significantly different after the recovery period. The myostatin/ -actin mRNA ratios (means ...) were higher in the muscles of the R1 rats compared with the control R5 rats: 5·0-fold in tibialis (5·35 1·85 vs 1·07 0·26), 3·0-fold in biceps (2·46 0·70 vs 0·81 0·04), 1·9-fold in quadriceps (7·84 1·73 vs 4·08 0·52), and 2·2-fold in gastrocnemius (0·99 0·35 vs 0·44 0·17). These values also normalized upon acclimatization. Our antibody against a myostatin peptide was validated by detection of the recombinant human myostatin protein on Western blots, which also showed that myostatin immunostaining was increased in muscle sections from R1 rats, compared with control R3 rats, and normalized upon acclimatization. In contrast, IGF-II mRNA concentrations in the muscles from R1 rats were 64-89% lower than those in R3 animals. With the exception of the gastrocnemius, IGF-II was also decreased in R5 animals maintained in flight-simulated cages, and normalized upon acclimatization. The intramuscular IGF-I mRNA levels were not significantly different between the spaceflight rats and the controls. No increase was found in the proteolysis markers 3-methyl histidine, ubiquitin mRNA, and proteasome 2C mRNA. In conclusion, the loss of skeletal muscle mass that occurs during spaceflight is associated with increased myostatin mRNA and protein levels in the skeletal muscle, and a decrease in IGF-II mRNA levels. These alterations are normalized upon restoration of normal gravity and caging conditions. These data suggest that reciprocal changes in the expression of myostatin and IGF-II may co...

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Section: Introductionmentioning

confidence: 99%

Myostatin and insulin-like growth factor-I and -II expression in the muscle of rats exposed to the microgravity environment of the NeuroLab space shuttle flight

Lalani

Bhasin²,

Byhower³

et al. 2000

Journal of Endocrinology

156

115

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“…In experiments using the rat hindlimb suspension model to mimic disuse atrophy experienced in space, the mass of soleus muscle exposed to anti-gravity conditions rapidly decreased to one half of initial values after one week. Shultz (Mozdziak et al 1998) and Edgerton's groups (Allen et al 1997) showed a decrease in muscle size and in the number of muscle cells, which likely reflects disuse-induced apoptosis of muscle cells. Although muscle cells are known to undergo size changes, the mechanisms by which disuse induces decreases in muscle size and apoptosis are unclear.…”

Section: Response Of Stress Protein 'B-crystallin In Muscles To Mechamentioning

confidence: 94%

Gravitational Effects on Human Physiology

Atomi

2015

Subcellular Biochemistry

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Physical working capacity decreases with age and also in microgravity. Regardless of age, increased physical activity can always improve the physical adaptability of the body, although the mechanisms of this adaptability are unknown. Physical exercise produces various mechanical stimuli in the body, and these stimuli may be essential for cell survival in organisms. The cytoskeleton plays an important role in maintaining cell shape and tension development, and in various molecular and/or cellular organelles involved in cellular trafficking. Both intra and extracellular stimuli send signals through the cytoskeleton to the nucleus and modulate gene expression via an intrinsic property, namely the "dynamic instability" of cytoskeletal proteins. αB-crystallin is an important chaperone for cytoskeletal proteins in muscle cells. Decreases in the levels of αB-crystallin are specifically associated with a marked decrease in muscle mass (atrophy) in a rat hindlimb suspension model that mimics muscle and bone atrophy that occurs in space and increases with passive stretch. Moreover, immunofluorescence data show complete co-localization of αB-crystallin and the tubulin/microtubule system in myoblast cells. This association was further confirmed in biochemical experiments carried out in vitro showing that αB-crystallin acts as a chaperone for heat-denatured tubulin and prevents microtubule disassembly induced by calcium. Physical activity induces the constitutive expression of αB-crystallin, which helps to maintain the homeostasis of cytoskeleton dynamics in response to gravitational forces. This relationship between chaperone expression levels and regulation of cytoskeletal dynamics observed in slow anti-gravitational muscles as well as in mammalian striated muscles, such as those in the heart, diaphragm and tongue, may have been especially essential for human evolution in particular. Elucidation of the intrinsic properties of the tubulin/microtubule and chaperone αB-crystallin protein complex systems is expected to provide valuable information for high-pressure bioscience and gravity health science.

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“…This phenomenon was closely associated with the inhibited increases of satellite cell and myonuclear number. It was also reported that gravitational unloading downregulates the satellite cell mitotic activity (11,(35)(36)(37)49). Furthermore, atrophy and regrowth of muscle fibers in soleus (59) and adductor longus (41) of Wistar Hannover rats were closely related to the number of satellite cells, which is also positively correlated with the distribution of myonuclei.…”

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confidence: 88%

Macrophage deficiency in osteopetrotic (op/op) mice inhibits activation of satellite cells and prevents hypertrophy in single soleus fibers

Ohira

Wang

Ito

et al. 2015

American Journal of Physiology-Cell Physiology

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Effects of macrophage on the responses of soleus fiber size to hind limb unloading and reloading were studied in osteopetrotic homozygous (op/op) mice with inactivated mutation of macrophage colony-stimulating factor (M-CSF) gene and in wild-type (ϩ/ϩ) and heterozygous (ϩ/op) mice. The basal levels of mitotically active and quiescent satellite cell (Ϫ46 and Ϫ39% vs. ϩ/ϩ, and Ϫ40 and Ϫ30% vs. ϩ/op) and myonuclear number (Ϫ29% vs. ϩ/ϩ and Ϫ28% vs. ϩ/op) in fibers of op/op mice were significantly less than controls. Fiber length and sarcomere number in op/op were also less than ϩ/ϩ (Ϫ22%) and ϩ/op (Ϫ21%) mice. Similar trend was noted in fiber cross-sectional area (CSA, Ϫ15% vs. ϩ/ϩ, P ϭ 0.06, and Ϫ14% vs. ϩ/op, P ϭ 0.07). The sizes of myonuclear domain, cytoplasmic volume per myonucleus, were identical in all types of mice. The CSA, length, and the whole number of sarcomeres, myonuclei, and mitotically active and quiescent satellite cells, as well as myonuclear domain, in single muscle fibers were decreased after 10 days of unloading in all types of mice, although all of these parameters in ϩ/ϩ and ϩ/op mice were increased toward the control values after 10 days of reloading. However, none of these levels in op/op mice were recovered. Data suggest that M-CSF and/or macrophages are important to activate satellite cells, which cause increase of myonuclear number during fiber hypertrophy. However, it is unclear why their responses to general growth and reloading after unloading are different. myonuclei; muscle fiber size; osteopetrotic mice; satellite cells; unloading and reloading SKELETAL MUSCLES ARE COMPOSED of multinucleated muscle fibers and have an extensive capacity for morphological and functional adaptation. For example, chronic unloading of muscles by bedrest in humans (45,46,64) and hind limb suspension and actual spaceflight in animals (6, 40 -42, 47, 59) result in muscle fiber atrophy and a shift toward a faster myosin heavy chain profile, particularly in antigravity muscles composed predominantly of slow-twitch fibers, such as the soleus (6,42,(45)(46)(47) and adductor longus (41, 59). Muscle fiber atrophy and the shift toward a faster myosin heavy chain profile are reversed in response to muscle reloading (41,45,46,59). The muscular response to reloading appears to be closely related to intramuscular stimuli that are activated by mechanical loading (20,21,41,47,59) and/or muscle activation with reloading (1,12,20,22,41).Macrophage colony-stimulating factor (M-CSF, CSF-1) is a cytokine that influences hematopoietic stem cells to differentiate into macrophages and other cell types (54). Deficiency of macrophages has been well-reported in osteopetrotic (op/op) mutant mice with inactivating mutation of M-CSF gene, which results in the absence of certain macrophage and in osteopetrosis, following a lack of osteoclasts (60, 63). Tidball and Wehling-Henricks (58) reported important roles of macrophages in the repair of muscle fiber membrane, regeneration, and regrowth after unloading-related atrophy in mouse s...

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Hindlimb suspension reduces muscle regeneration

Cited by 38 publications

References 17 publications

Myostatin and insulin-like growth factor-I and -II expression in the muscle of rats exposed to the microgravity environment of the NeuroLab space shuttle flight

Myostatin and insulin-like growth factor-I and -II expression in the muscle of rats exposed to the microgravity environment of the NeuroLab space shuttle flight

Gravitational Effects on Human Physiology

Macrophage deficiency in osteopetrotic (op/op) mice inhibits activation of satellite cells and prevents hypertrophy in single soleus fibers

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