Myostatin Mediates Quadriceps Muscle Atrophy And Fibrosis Rapidly After ACL Transection In Novel Murine Model

Many patients with anterior cruciate ligament (ACL) injuries have persistent quadriceps muscle atrophy, even after considerable time in rehabilitation. Understanding the factors that regulate muscle mass, and the time course of atrophic events, is important for identifying therapeutic interventions. Using a non-invasive animal model of ACL injury, a longitudinal study was performed to elucidate key parameters underlying quadriceps muscle atrophy. Male Long-Evans rats were euthanized at 6, 12, 24, 48-hrs and 1, 2, 4-wks after ACL injury that was induced via tibial compression overload; controls were not injured. Vastus Lateralis muscle size was determined by wet weight and fiber CSA. Evidence of disrupted neuromuscular communication was assessed via the expression of NCAM and genes associated with denervation and neuromuscular junction instability. Abundance of MuRF-1, MAFbx, and 45s pre-rRNA along with 20S proteasome activity were determined to investigate mechanisms related to muscle atrophy. Lastly, muscle damage-related parameters were assessed by measuring IgG permeability, centronucleation, CD68 mRNA and satellite cell abundance. Compared to controls, we observed a greater percentage of NCAM positive fibers at 6-hrs post-injury, followed by higher MAFbx abundance 48-hrs post-injury, and higher 20S proteasome activity at 1-wk post-injury. A loss of muscle wet weight, smaller fiber CSA and the elevated expression of Runx1 were also observed at the 1-wk post-injury time point relative to controls. There also were no differences observed in any damage markers. These results indicate that alterations in neuromuscular communication precede the upregulation of atrophic factors that regulate quadriceps muscle mass early after non-invasive ACL injury.

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The Effects of Anterior Cruciate Ligament Reconstruction on Individual Quadriceps Muscle Thickness and Circulating Biomarkers

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph16244895 ◽

2019 ◽

Vol 16 (24) ◽

pp. 4895 ◽

Cited By ~ 2

Author(s):

Jae-Ho Yang ◽

Seung-Pyo Eun ◽

Dong-Ho Park ◽

Hyo-Bum Kwak ◽

Eunwook Chang

Keyword(s):

Anterior Cruciate Ligament ◽

Anterior Cruciate Ligament Reconstruction ◽

Muscle Atrophy ◽

Ligament Reconstruction ◽

Cruciate Ligament ◽

Muscle Thickness ◽

Quadriceps Muscle ◽

Circulating Biomarkers ◽

Cruciate Ligament Reconstruction ◽

Anterior Cruciate

Anterior cruciate ligament reconstruction (ACLR) frequently results in quadriceps atrophy. The present study investigated the effect of ACLR on the muscle thickness of the different constituent muscles of the quadriceps and circulating biomarkers related to muscle atrophy and hypertrophy. Fourteen subjects underwent anterior cruciate ligament reconstruction following injury. Quadriceps muscle thicknesses were measured using ultrasound, and circulating biomarkers in the blood were measured using enzyme-linked immunosorbent assays (ELISAs) at the preoperative visit (PRE) and at two postoperative visits (PO1, PO2) in the early stages post-surgery. Differences between time points were analyzed using one-way repeated measures analysis of variance (ANOVA) tests. The most important finding was that severe muscle atrophy occurred in the vastus intermedius (VI) after ACLR (PRE: 20.45 ± 6.82 mm, PO1: 16.05 ± 6.13 mm, PO2: 13.18 ± 4.7 mm, F = 59.0, p < 0.001). Furthermore, the myostatin level was slightly increased, and IGF-1 was significantly reduced throughout the entire period. Therefore, we suggest that inducing selective hypertrophy in the vastus intermedius during the process of rehabilitation would be important for athletes and individuals who engage in explosive sports. Moreover, inhibiting myostatin level increases and maintaining IGF-1 levels in the early phase of recovery after ACLR to prevent muscle atrophy may provide a pharmaceutical option for rehabilitation after anterior cruciate ligament injury.

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Exercise interrupts ongoing glucocorticoid-induced muscle atrophy and glutamine synthetase induction

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1992.263.6.e1157 ◽

1992 ◽

Vol 263 (6) ◽

pp. E1157-E1163 ◽

Cited By ~ 2

Author(s):

M. T. Falduto ◽

A. P. Young ◽

R. C. Hickson

Keyword(s):

Enzyme Activity ◽

Glutamine Synthetase ◽

Muscle Atrophy ◽

Contractile Activity ◽

Hormone Treatment ◽

Quadriceps Muscle ◽

Treadmill Running ◽

Female Rats ◽

Glucocorticoid Treatment ◽

Fast Twitch

This study was undertaken to determine whether regular endurance exercise is a deterrent to a developing state of muscle atrophy from glucocorticoids and to evaluate whether the contractile activity antagonizes the hormonal actions on glutamine synthetase, alanine aminotransferase, and cytosolic aspartate aminotransferase (cAspAT). Adult female rats were administered cortisol acetate (CA, 100 mg/kg body wt) or an equal volume of the vehicle solution for up to 15 days. Exercise (treadmill running at 31 m/min, 10% grade, 90 min/day) was introduced after 4 days of CA treatment, at which time plantaris and quadriceps muscle mass had been reduced to 90% of control levels. Running for 11 consecutive days prevented 40 mg of the 90-mg loss and 227 mg of the 808-mg loss that were subsequently observed in plantaris and quadriceps muscles, respectively, in the sedentary animals. Glutamine synthetase mRNA and enzyme activity were elevated threefold by glucocorticoid treatment in the deep quadriceps (fast-twitch red) muscles after 4 days. Initiating exercise completely interfered with the further hormonal induction (to approximately 5-fold) of this enzyme and, after 11 consecutive days of the exercise regimen, glutamine synthetase mRNA and enzyme activity were 58 and 68% of values from CA-treated sedentary animals. In vehicle-treated groups, basal levels of glutamine synthetase expression were also diminished by exercise to approximately 40% of the values in sedentary controls. Hormone treatment did not alter either aminotransferase enzyme activity but reduced cAspAT mRNA in fast-twitch red muscles by 50%. Exercise abolished the glucocorticoid effect on cAspAT mRNA.(ABSTRACT TRUNCATED AT 250 WORDS)

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Preclinical Evaluation of a Food-Derived Functional Ingredient to Address Skeletal Muscle Atrophy

Nutrients ◽

10.3390/nu12082274 ◽

2020 ◽

Vol 12 (8) ◽

pp. 2274

Author(s):

Roi Cal ◽

Heidi Davis ◽

Alish Kerr ◽

Audrey Wall ◽

Brendan Molloy ◽

...

Keyword(s):

Skeletal Muscle ◽

Muscle Atrophy ◽

Soleus Muscle ◽

Murine Model ◽

The Body ◽

Skeletal Muscle Atrophy ◽

Type I ◽

Disuse Atrophy ◽

Tnf Α

Skeletal muscle is the metabolic powerhouse of the body, however, dysregulation of the mechanisms involved in skeletal muscle mass maintenance can have devastating effects leading to many metabolic and physiological diseases. The lack of effective solutions makes finding a validated nutritional intervention an urgent unmet medical need. In vitro testing in murine skeletal muscle cells and human macrophages was carried out to determine the effect of a hydrolysate derived from vicia faba (PeptiStrong: NPN_1) against phosphorylated S6, atrophy gene expression, and tumour necrosis factor alpha (TNF-α) secretion, respectively. Finally, the efficacy of NPN_1 on attenuating muscle waste in vivo was assessed in an atrophy murine model. Treatment of NPN_1 significantly increased the phosphorylation of S6, downregulated muscle atrophy related genes, and reduced lipopolysaccharide-induced TNF-α release in vitro. In a disuse atrophy murine model, following 18 days of NPN_1 treatment, mice exhibited a significant attenuation of muscle loss in the soleus muscle and increased the integrated expression of Type I and Type IIa fibres. At the RNA level, a significant upregulation of protein synthesis-related genes was observed in the soleus muscle following NPN_1 treatment. In vitro and preclinical results suggest that NPN_1 is an effective bioactive ingredient with great potential to prolong muscle health.

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Temporal development of muscle atrophy in murine model of arthritis is related to disease severity

Journal of Cachexia Sarcopenia and Muscle ◽

10.1007/s13539-013-0102-1 ◽

2013 ◽

Vol 4 (3) ◽

pp. 231-238 ◽

Cited By ~ 16

Author(s):

Lidiane I. Filippin ◽

Vivian N. Teixeira ◽

Paula R. Viacava ◽

Priscila S. Lora ◽

Laura L. Xavier ◽

...

Keyword(s):

Disease Severity ◽

Muscle Atrophy ◽

Murine Model ◽

Temporal Development

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Tumor necrosis factor-like weak inducer of apoptosis regulates quadriceps muscle atrophy and fiber-type alteration in a rat model of chronic obstructive pulmonary disease

Tobacco Induced Diseases ◽

10.1186/s12971-017-0148-5 ◽

2017 ◽

Vol 15 (1) ◽

Cited By ~ 5

Author(s):

Jun-Juan Lu ◽

Qing Wang ◽

Li Hua Xie ◽

Qiang Zhang ◽

Sheng Hua Sun

Keyword(s):

Chronic Obstructive Pulmonary Disease ◽

Tumor Necrosis Factor ◽

Muscle Atrophy ◽

Rat Model ◽

Tumor Necrosis ◽

Fiber Type ◽

Quadriceps Muscle ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

Necrosis Factor

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Muscle Atrophy and Functional Deficits of Knee Extensors and Flexors in People With Chronic Stroke

Physical Therapy ◽

10.2522/ptj.20090127 ◽

2012 ◽

Vol 92 (3) ◽

pp. 429-439 ◽

Cited By ~ 26

Author(s):

Christiane L. Prado-Medeiros ◽

Milla P. Silva ◽

Giovanna C. Lessi ◽

Marcela Z. Alves ◽

Alberto Tannus ◽

...

Keyword(s):

Motor Function ◽

Muscle Atrophy ◽

Peak Torque ◽

Quadriceps Muscle ◽

Chronic Stroke ◽

Muscle Volume ◽

Knee Extensors ◽

Control Group ◽

Hamstring Muscle ◽

Paretic Limb

BackgroundFurther clarification is needed with regard to the degree of atrophy in individual muscle groups and its possible relationship to joint torque deficit poststroke.ObjectiveThe purpose of this study was to investigate quadriceps and hamstring muscle volume and strength deficits of the knee extensors and flexors in people with chronic hemiparesis compared with a control group.DesignThis was a cross-sectional study.MethodsThirteen individuals with hemiparesis due to chronic stroke (hemiparetic group) and 13 individuals who were healthy (control group) participated in this study. Motor function, quadriceps and hamstring muscle volume, and maximal concentric and eccentric contractions of the knee extensors and flexors were assessed.ResultsOnly the quadriceps muscle of the paretic limb showed reduced muscle volume (24%) compared with the contralateral (nonparetic) limb. There were no differences in muscle volume between the hemiparetic and control groups. The peak torque of the paretic-limb knee extensors and flexors was reduced in both contraction modes and velocities compared with the nonparetic limb (36%–67%) and with the control group (49%–75%). The nonparetic limb also showed decreased extensor and flexor peak torque compared with the control group (17%–23%). Power showed similar deficits in strength (12%–78%). There were significant correlations between motor function and strength deficits (.54–.67).LimitationsMagnetic resonance imaging coil length did not allow measurement of the proximal region of the thigh.ConclusionsThere were different responses between quadriceps and hamstring muscle volumes in the paretic limb that had quadriceps muscle atrophy only. However, both paretic and nonparetic limbs showed knee extensor and flexor torque and power reduction.

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The Relationship Between Quadriceps Muscle Atrophy and Proprioception Function in Knee Osteoarthritis Patients

Surabaya Physical Medicine and Rehabilitation Journal ◽

10.20473/spmrj.v1i2.16177 ◽

2019 ◽

Vol 1 (2) ◽

pp. 59

Author(s):

Ayu Susanti ◽

Rr. Indrayuni Lukitra Wardhani ◽

I Putu Alit Pawana

Keyword(s):

Knee Osteoarthritis ◽

Pain Intensity ◽

Muscle Atrophy ◽

Quadriceps Muscle ◽

Joint Position Sense ◽

Osteoarthritis Of The Knee ◽

Cross Sectional ◽

Knee Oa ◽

Proprioceptive Function ◽

The Relationship

Background: Osteoarthritis of the knee (OA) patients can experience impaired proprioceptive function which causes instability, balance disorder and limited activity. Further analysis is needed to detect changes that occur. There are two methods to evaluate the speed and angle of a particular motion as an analysis of the function of proprioception, Time to Detect Passive Movements (TTDPM) and Joint Position Sense (JPS).Aim: To analyze the relationship between quadriceps muscle atrophy with proprioception in knee osteoarthritis patients.Methods: The design of this research is cross sectional analysis done in Dr. Soetomo General Hospital Surabaya, Indonesia. There were 25 knee OA patients (2 men and 23 women) with each subject had proprioception (JPS and TTDPM) function measured using isokinetics dynamometer on both sides of the knee.Results: This study shows the atrophic side had greater pain intensity and greater disturbance of proprioception. In addition, there were significant differences in JPS measurements at angle of 30⁰, and 60⁰ and TTDPM (p <0.05). No difference obtained at 45⁰ measurements angle.Conclusion: In this study, there was no association between quadriceps atrophy and function of proprioception in knee osteoarthritis patients. This was due to a number of confounding factors that cannot be controlled such as duration, difference in pain intensity, OA severity, physical activity before measurement, and fatigue which can affect proprioception function and bring misinterpretation on measurements.

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Exercise interrupts ongoing glucocorticoid-induced muscle atrophy and glutamine synthetase induction

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.2006.263.6.e1157 ◽

2006 ◽

Vol 263 (6) ◽

pp. E1157-E1163

Author(s):

M. T. Falduto ◽

A. P. Young ◽

R. C. Hickson

Keyword(s):

Enzyme Activity ◽

Glutamine Synthetase ◽

Muscle Atrophy ◽

Contractile Activity ◽

Hormone Treatment ◽

Quadriceps Muscle ◽

Treadmill Running ◽

Female Rats ◽

Glucocorticoid Treatment ◽

Fast Twitch

This study was undertaken to determine whether regular endurance exercise is a deterrent to a developing state of muscle atrophy from glucocorticoids and to evaluate whether the contractile activity antagonizes the hormonal actions on glutamine synthetase, alanine aminotransferase, and cytosolic aspartate aminotransferase (cAspAT). Adult female rats were administered cortisol acetate (CA, 100 mg/kg body wt) or an equal volume of the vehicle solution for up to 15 days. Exercise (treadmill running at 31 m/min, 10% grade, 90 min/day) was introduced after 4 days of CA treatment, at which time plantaris and quadriceps muscle mass had been reduced to 90% of control levels. Running for 11 consecutive days prevented 40 mg of the 90-mg loss and 227 mg of the 808-mg loss that were subsequently observed in plantaris and quadriceps muscles, respectively, in the sedentary animals. Glutamine synthetase mRNA and enzyme activity were elevated threefold by glucocorticoid treatment in the deep quadriceps (fast-twitch red) muscles after 4 days. Initiating exercise completely interfered with the further hormonal induction (to approximately 5-fold) of this enzyme and, after 11 consecutive days of the exercise regimen, glutamine synthetase mRNA and enzyme activity were 58 and 68% of values from CA-treated sedentary animals. In vehicle-treated groups, basal levels of glutamine synthetase expression were also diminished by exercise to approximately 40% of the values in sedentary controls. Hormone treatment did not alter either aminotransferase enzyme activity but reduced cAspAT mRNA in fast-twitch red muscles by 50%. Exercise abolished the glucocorticoid effect on cAspAT mRNA.(ABSTRACT TRUNCATED AT 250 WORDS)

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