scholarly journals Evaluation of skeletal muscle regeneration in experimental model after malnutrition

2017 ◽  
Vol 77 (1) ◽  
pp. 83-91 ◽  
Author(s):  
A. Pertille ◽  
K. F. Moura ◽  
C. Y. Matsumura ◽  
R. Ferretti ◽  
D. M. Ramos ◽  
...  
Keyword(s):  
Muscle Regeneration ◽  
Tibialis Anterior ◽  
Tibialis Anterior Muscle ◽  
Recovery Period ◽  
Protein Diet ◽  
Skeletal Muscle Regeneration ◽  
Post Injury ◽  
Cross Sectional ◽  
Young Rats ◽  
Normal Protein Diet

Abstract The aim of this study was to analyze muscle regeneration after cryoinjury in the tibialis anterior muscle of young rats that were malnourished and then recovered. Forty Wistar rats were divided into a nourished group that received a normal protein diet (14% casein) for 90 days and a malnourished and recovered rats group (MR) that was submitted to 45 days of malnutrition with a hypoproteic diet (6% casein) followed by 45 days of a normal protein diet (14% casein). After the recovery period, all of the animals underwent cryoinjury in the right tibialis anterior muscle and euthanasia after 7, 14 and 21 days. The amount of connective tissue and the inflammation area was higher in the malnutrition recovered injury MR group (MRI) at 14 days post-injury (p < 0.05). Additionally, the cross-sectional area (CSA) of the regenerated fibers was decreased in the MRI (p < 0.05). The MyoD and myogenin protein levels were higher in the nourished injury group. Similar levels of TGF-β1 were found between groups. The proposed malnutrition protocol was effective in showing delayed changes in the regeneration process of the tibialis anterior muscle of young rats. Furthermore, we observed a delay in muscle repair even after nutritional recovery.

Inactivation of PPARβ/δ adversely affects satellite cells and reduces postnatal myogenesis

2015 ◽  
Vol 309 (2) ◽  
pp. E122-E131 ◽  
Author(s):  
Preeti Chandrashekar ◽  
Ravikumar Manickam ◽  
Xiaojia Ge ◽  
Sabeera Bonala ◽  
Craig McFarlane ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Satellite Cell ◽  
Satellite Cells ◽  
Muscle Regeneration ◽  
Tibialis Anterior ◽  
Tibialis Anterior Muscle ◽  
Skeletal Muscle Regeneration ◽  
Muscle Weight ◽  
Cross Sectional ◽  
Postnatal Myogenesis

Peroxisome proliferator-activated receptor β/δ ( PPARβ/δ) is a ubiquitously expressed gene with higher levels observed in skeletal muscle. Recently, our laboratory showed (Bonala S, Lokireddy S, Arigela H, Teng S, Wahli W, Sharma M, McFarlane C, Kambadur R. J Biol Chem 287: 12935–12951, 2012) that PPARβ/δ modulates myostatin activity to induce myogenesis in skeletal muscle. In the present study, we show that PPARβ/δ-null mice display reduced body weight, skeletal muscle weight, and myofiber atrophy during postnatal development. In addition, a significant reduction in satellite cell number was observed in PPARβ/δ-null mice, suggesting a role for PPARβ/δ in muscle regeneration. To investigate this, tibialis anterior muscles were injured with notexin, and muscle regeneration was monitored on days 3, 5, 7, and 28 postinjury. Immunohistochemical analysis revealed an increased inflammatory response and reduced myoblast proliferation in regenerating muscle from PPARβ/δ-null mice. Histological analysis confirmed that the regenerated muscle fibers of PPARβ/δ-null mice maintained an atrophy phenotype with reduced numbers of centrally placed nuclei. Even though satellite cell numbers were reduced before injury, satellite cell self-renewal was found to be unaffected in PPARβ/δ-null mice after regeneration. Previously, our laboratory had showed (Bonala S, Lokireddy S, Arigela H, Teng S, Wahli W, Sharma M, McFarlane C, Kambadur R. J Biol Chem 287: 12935–12951, 2012) that inactivation of PPARβ/δ increases myostatin signaling and inhibits myogenesis. Our results here indeed confirm that inactivation of myostatin signaling rescues the atrophy phenotype and improves muscle fiber cross-sectional area in both uninjured and regenerated tibialis anterior muscle from PPARβ/δ-null mice. Taken together, these data suggest that absence of PPARβ/δ leads to loss of satellite cells, impaired skeletal muscle regeneration, and postnatal myogenesis. Furthermore, our results also demonstrate that functional antagonism of myostatin has utility in rescuing these effects.

scholarly journals Septin-7 is indispensable in skeletal muscle regeneration

2021 ◽  
Vol 154 (9) ◽  
Author(s):  
Andrea Telek ◽  
Janos Fodor ◽  
Nora Dobrosi ◽  
Laszlo Szabo ◽  
Monika Gönczi ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Cell Division ◽  
Mrna Expression ◽  
Muscle Regeneration ◽  
Tibialis Anterior ◽  
Tibialis Anterior Muscle ◽  
Critical Role ◽  
Skeletal Muscle Regeneration ◽  
The Right

Septins are considered as the fourth component of the cytoskeleton, with septin-7 isoform playing a critical role in myogenic cell division and fusion. Skeletal muscle regeneration is a highly orchestrated process that requires many steps, including proper cell division to achieve functional recovery. Here, the role of septin-7 was investigated in this complex process. To this end, muscle injury was induced in wild type BL6/C57 and septin-7–conditional (mer-Cre-mer) knock-down mice by in vivo BaCl2 injection to the left m. tibialis anterior muscle (TA) of the mice (the right m. tibialis anterior muscle was nontreated control). Mice were sacrificed 4 and 14 d later to reflect the early (monitored by PAX7 level) and late (monitored by myogenin level) phases of muscle regeneration. Western blotting was used to follow the changes of septin-7, PAX7, and myogenin expression at the protein level, while changes of mRNA were detected by qPCR. Morphological differences were visualized by HE staining. Levels of septin-7 protein increased 4 and 14 d after injury in BL6/C57 mice and mRNA expression of SEPT7 showed significant elevation both 4 and 14 d after injection in Cre+ mice only, considered to be a compensatory increase of mRNA expression of SEPT7 in order to ensure the appropriate regeneration process. Furthermore, up-regulation of septin-7 protein was more pronounced on day 14 in both Cre− and Cre+ mice, which may indicate its importance in the later phase of regeneration. Level of PAX7 and myogenin were also increased 4 and 14 d after injury in BL6/C57, Cre−, and Cre+ mice, respectively. Taken together, our data suggest the importance of septin-7 in skeletal muscle regeneration.

scholarly journals Loss of Parkin Results in Altered Muscle Stem Cell Differentiation during Regeneration

2020 ◽  
Vol 21 (21) ◽  
pp. 8007
Author(s):  
Marcos V. Esteca ◽  
Matheus B. Severino ◽  
João G. Silvestre ◽  
Gustavo Palmeira dos Santos ◽  
Letícia Tamborlin ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Regeneration ◽  
High Capacity ◽  
Stem Cell Differentiation ◽  
Skeletal Muscle Regeneration ◽  
Post Injury ◽  
Cross Sectional ◽  
Myoblast Cell Line ◽  
Myoblast Cell

The high capacity of the skeletal muscle to regenerate is due to the presence of muscle stem cells (MuSCs, or satellite cells). The E3 ubiquitin ligase Parkin is a key regulator of mitophagy and is recruited to mitochondria during differentiation of mouse myoblast cell line. However, the function of mitophagy during regeneration has not been investigated in vivo. Here, we have utilized Parkin deficient (Parkin–/–) mice to investigate the role of Parkin in skeletal muscle regeneration. We found a persistent deficiency in skeletal muscle regeneration in Parkin–/– mice after cardiotoxin (CTX) injury with increased area of fibrosis and decreased cross-sectional area (CSA) of myofibres post-injury. There was also a significant modulation of MuSCs differentiation and mitophagic markers, with altered mitochondrial proteins during skeletal muscle regeneration in Parkin–/– mice. Our data suggest that Parkin-mediated mitophagy plays a key role in skeletal muscle regeneration and is necessary for MuSCs differentiation.

Hyperthyroidism impairs early repair in normal but not dystrophic mdx mouse tibialis anterior muscle. An in vivo study

1996 ◽  
Vol 74 (3) ◽  
pp. 315-324 ◽  
Author(s):  
A. N. Pernitsky ◽  
L. M. McIntosh ◽  
J. E. Anderson
Keyword(s):  
Muscle Regeneration ◽  
Tibialis Anterior ◽  
Mononuclear Cells ◽  
Strain Difference ◽  
Tibialis Anterior Muscle ◽  
Mdx Mouse ◽  
Mdx Mice ◽  
Cross Sectional ◽  
Fiber Damage

The effect of hyperthyroidism on muscle repair was examined in mdx and control mice injected with triiodothyronine (T3) for 4 weeks. On day 24 of treatment, the right tibialis anterior (TA) muscle was crush-injured; 3 days later, mice received intraperitoneal [3H]thymidine to label newly synthesized DNA. One day later, muscles from both limbs were removed to study the severity of dystrophy (uncrushed muscle) and the regeneration response (crushed muscle). In uncrushed TA muscle, the area of active dystrophy (fiber damage and infiltration as a proportion of muscle cross-sectional area) was reduced by half after T3 treatment. Uncrushed muscle fiber diameter was lower in T3-treated control muscles. In crushed muscles, the diameter of new myotubes was larger in mdx mice than in controls and was reduced after T3 treatment in control regenerating muscle. In the same muscles, developmental myosin heavy chain was present in new myotubes and in small numbers of mononuclear cells (possibly differentiating myoblasts) near new myotubes and surviving fibers. Myotube density in the regenerating muscles was not changed by T3 treatment, although the number of myotube nuclei per field was decreased in control and increased in mdx T3-treated mice. Results extend previous reports of T3 effects on dystrophy and the strain difference in muscle precursor cell (mpc) proliferation. The results also suggest the hypothesis that excess T3 affects muscle regeneration either by reducing mpc proliferation or by increasing mpc fusion early in regeneration in control and mdx muscle.Key words: hypothyroid, muscle regeneration, crush injury, proliferation, mdx mouse.

scholarly journals A High Protein Diet Does Not Improve Protein Synthesis in the Nonweight-Bearing Rat Tibialis Anterior Muscle

1996 ◽  
Vol 126 (1) ◽  
pp. 266-272 ◽  
Author(s):  
Daniel Taillandier ◽  
Charles-Yannick Guezennec ◽  
Philippe Patureau-Mirand ◽  
Xavier Bigard ◽  
Maurice Arnal ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Tibialis Anterior ◽  
Tibialis Anterior Muscle ◽  
High Protein Diet ◽  
High Protein ◽  
Protein Diet

scholarly journals Conditional Deletion of Dicer in Adult Mice Impairs Skeletal Muscle Regeneration

2019 ◽  
Vol 20 (22) ◽  
pp. 5686 ◽  
Author(s):  
Satoshi Oikawa ◽  
Minjung Lee ◽  
Takayuki Akimoto
Keyword(s):  
Skeletal Muscle ◽  
Muscle Regeneration ◽  
Myogenic Differentiation ◽  
Tibialis Anterior Muscle ◽  
Critical Factor ◽  
Skeletal Muscle Regeneration ◽  
Small Noncoding Rnas ◽  
Adult Mice

Skeletal muscle has a remarkable regenerative capacity, which is orchestrated by multiple processes, including the proliferation, fusion, and differentiation of the resident stem cells in muscle. MicroRNAs (miRNAs) are small noncoding RNAs that mediate the translational repression or degradation of mRNA to regulate diverse biological functions. Previous studies have suggested that several miRNAs play important roles in myoblast proliferation and differentiation in vitro. However, their potential roles in skeletal muscle regeneration in vivo have not been fully established. In this study, we generated a mouse in which the Dicer gene, which encodes an enzyme essential in miRNA processing, was knocked out in a tamoxifen-inducible way (iDicer KO mouse) and determined its regenerative potential after cardiotoxin-induced acute muscle injury. Dicer mRNA expression was significantly reduced in the tibialis anterior muscle of the iDicer KO mice, whereas the expression of muscle-enriched miRNAs was only slightly reduced in the Dicer-deficient muscles. After cardiotoxin injection, the iDicer KO mice showed impaired muscle regeneration. We also demonstrated that the number of PAX7+ cells, cell proliferation, and the myogenic differentiation capacity of the primary myoblasts did not differ between the wild-type and the iDicer KO mice. Taken together, these data demonstrate that Dicer is a critical factor for muscle regeneration in vivo.

The worsening of tibialis anterior muscle atrophy during recovery post-immobilization correlates with enhanced connective tissue area, proteolysis, and apoptosis

2012 ◽  
Vol 303 (11) ◽  
pp. E1335-E1347 ◽  
Author(s):  
Lamia Slimani ◽  
Didier Micol ◽  
Julien Amat ◽  
Geoffrey Delcros ◽  
Bruno Meunier ◽  
...  
Keyword(s):  
Connective Tissue ◽  
Muscle Atrophy ◽  
Tibialis Anterior ◽  
Fiber Type ◽  
Tibialis Anterior Muscle ◽  
Recovery Period ◽  
Mrna Levels ◽  
Adult Rats ◽  
Extracellular Compartment ◽  
Nuclear Apoptosis

Sustained muscle wasting due to immobilization leads to weakening and severe metabolic consequences. The mechanisms responsible for muscle recovery after immobilization are poorly defined. Muscle atrophy induced by immobilization worsened in the lengthened tibialis anterior (TA) muscle but not in the shortened gastrocnemius muscle. Here, we investigated some mechanisms responsible for this differential response. Adult rats were subjected to unilateral hindlimb casting for 8 days (I8). Casts were removed at I8, and animals were allowed to recover for 10 days (R1 to R10). The worsening of TA atrophy following immobilization occurred immediately after cast removal at R1 and was sustained until R10. This atrophy correlated with a decrease in type IIb myosin heavy chain (MyHC) isoform and an increase in type IIx, IIa, and I isoforms, with muscle connective tissue thickening, and with increased collagen (Col) I mRNA levels. Increased Col XII, Col IV, and Col XVIII mRNA levels during TA immobilization normalized at R6. Sustained enhanced peptidase activities of the proteasome and apoptosome activity contributed to the catabolic response during the studied recovery period. Finally, increased nuclear apoptosis prevailed only in the connective tissue compartment of the TA. Altogether, the worsening of the TA atrophy pending immediate reloading reflects a major remodeling of its fiber type properties and alterations in the structure/composition of the extracellular compartment that may influence its elasticity/stiffness. The data suggest that sustained enhanced ubiquitin-proteasome-dependent proteolysis and apoptosis are important for these adaptations and provide some rationale for explaining the atrophy of reloaded muscles pending immobilization in a lengthened position.

scholarly journals EFFECTS OF BETA-HYDROXY-BETA-METHYL BUTYRATE IN MUSCLE REGENERATION OF RATS

2018 ◽  
Vol 24 (2) ◽  
pp. 112-116
Author(s):  
Larissa Antunes ◽  
André Katayama Yamada ◽  
Adriana Pertille
Keyword(s):  
Muscle Regeneration ◽  
Tibialis Anterior ◽  
Calcium Supplementation ◽  
Tibialis Anterior Muscle ◽  
Intervention Group ◽  
Regeneration Process ◽  
Concentration Data ◽  
Level Of Evidence ◽  
Muscle Weight ◽  
Methyl Butyrate

ABSTRACT Introduction: Studies have shown that beta-hydroxy-beta-methyl butyrate (HMB) supplementation increases muscle strength and mass. Objective: To evaluate the effect of HMB supplementation on the muscle regeneration process in young and sedentary rats. Methods: Twenty-four male Wistar rats two months old were divided into two groups: lesion (LE) and supplemented (S), and evaluated in two moments - seven days (LE7; S7, n=6) and 21 days (LE21; S21, n=6). The right tibialis anterior muscle was subjected to cryolesion in all animals. After the injury, the LE group remained in the vivarium without any intervention. Group S received HMB calcium supplementation diluted in water by gavage (320 mg/kg/weight per day). The injury tibialis anterior (ITA), the tibialis anterior (TA), and the left soleus (SOL) muscles were removed, weighted and divided transversally into two parts, one for the analysis of the cross-sectional area (CSA) and the area of inflammation/regeneration and the other part to measure the muscular glycogen concentration. Data were evaluated using the SAS program considering mean and standard deviation. For analysis of variance the ANOVA test was used followed by the Tukey-HSD test (p≤0.05). Results: The ITA muscle weight was higher in S21 compared to S7 (p<0.05). The groups LE21 and S21 presented greater CSA of muscle fibers area and smaller ITA regeneration/inflammation area (p<0.05) when compared with the LE7 and S7 groups. There was an increase in muscle glycogen levels in S7 group compared to LE7 and S21 groups for TA and SOL (p<0.01), as well as in S21 group compared to LE21 for SOL (p<0.05). Conclusion: HMB did not influence the muscle regeneration process and did not favor anabolic activity in the different muscular fibers of young sedentary rats. Level of Evidence II; Therapeutic studies - Investigation of treatment results.

Sign in / Sign up

Export Citation Format

Share Document