Exercise and Tendon Remodeling Mechanism

Tendons connect muscles to bones and transmit the force exerted by the corresponding muscle to the skeleton and, therefore, are key components for locomotion. They are responsive to mechanical factors, which are essential for cellular functioning, tendon development, homeostasis, and repairing. Mechanical signals are transduced via molecular signaling pathways which trigger tendon adaptive responses. Previous data have already shown that exercise training promotes physiological adaptive responses, such as morphological properties and biomechanical and biochemical adaptations

Exercise Prevents Diaphragm Wasting Induced by Cigarette Smoke through Modulation of Antioxidant Genes and Metalloproteinases

Background. The present study aimed to analyze the effects of physical training on an antioxidant canonical pathway and metalloproteinases activity in diaphragm muscle in a model of cigarette smoke-induced chronic obstructive pulmonary disease (COPD). Methods. Male mice were randomized into control, smoke, exercise, and exercise + smoke groups, which were maintained in trial period of 24 weeks. Gene expression of kelch-like ECH-associated protein 1nuclear factor erythroid-2 like 2and heme-oxygenase1 by polymerase chain reaction was performed. Metalloproteinases 2 and 9 activities were analyzed by zymography. Exercise capacity was evaluated by treadmill exercise test before and after the protocol. Results. Aerobic training inhibited diaphragm muscle wasting induced by cigarette smoke exposure. This inhibition was associated with improved aerobic capacity in those animals that were submitted to 24 weeks of aerobic training, when compared to the control and smoke groups, which were not submitted to training. The aerobic training also downregulated the increase of matrix metalloproteinases (MMP-2 and MMP-9) and upregulated antioxidant genes, such as nuclear factor erythroid-2 like 2 (NRF2) and heme-oxygenase1 (HMOX1), in exercise + smoke group compared to smoke group. Conclusions. Treadmill aerobic training protects diaphragm muscle wasting induced by cigarette smoke exposure involving upregulation of antioxidant genes and downregulation of matrix metalloproteinases.CAPES (Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior)Sao Paulo Research Foundation (FAPESP) Grant [2012/15165-2]Univ Brasilia, Phys Therapy Div, Brasilia, DF, BrazilUniv Paulista, Dept Phys Therapy, Brasilia, DF, BrazilUniv Sao Paulo, Sch Med, Dept Med LIM 20, Sao Paulo, SP, BrazilFed Univ Sao Paulo UNIFESP, Postgrad Program Sci Human Movement & Rehabil, Av Ana Costa 95, BR-11060001 Santos, SP, BrazilUniv Fed Sao Carlos, Dept Phys Therapy, Sao Carlos, SP, BrazilUniv Brasil, Postgrad Program Bioengn, Rua Carolina Fonseca 235, BR-08230030 Sao Paulo, SP, BrazilBrazilian Inst Teaching & Res Pulm & Exercise Imm, Rua Pedro Ernesto 240, BR-12245520 Sao Jose Dos Campos, SP, BrazilUniv Brasilia, Phys Therapy Div, Brasilia, DF, BrazilFed Univ Sao Paulo UNIFESP, Postgrad Program Sci Human Movement & Rehabil, Av Ana Costa 95, BR-11060001 Santos, SP, BrazilFAPESP [2012/15165-2]Web of Scienc

Effects of thyroid hormone (T3) on Mdm2 E3 ligase expression and its implications in the muscle trofism regulation.

Estudos preliminares através de microarray nos mostraram que a E3 ligase Mdm2 foi regulado positivamente no músculo de animais hipertireoideos. Dessa forma, nós inferimos uma possível relação de Mdm2 com a atrofia causada por T3. Para testar nossa hipótese, ratos foram induzidos ao hipertireoidismo para análises subsequentes. Concomitante com a perda de massa muscular foi confirmado um aumento da expressão de Mdm2 tanto no nível gênico (p<0.05) quanto protéico. Interessantemente, Mdm2 foi preferencialmente expresso em fibras tipo I, mostrando maior sensibilidade dessas fibras ao T3. Além disso, foi observado uma diminuição severa na expressão de Pax7/MyoD associado à superexpressão de Mdm2, sugerindo inatividade das células satélites. Surpreendentemente, a inibição de Mdm2 em miotubos cultivados provocou uma diminuição severa no diâmetro destes (~35%, p<0.05), ou seja, tal inibição foi incapaz de minimizar a proteólise muscular causada por T3. Portanto, nós concluímos que a responsividade de Mdm2 ao T3 agiria como um mecanismo compensatório numa tentativa de minimizar a proteólise muscular causada pelo hipertireoidismo. Esta conclusão é reforçada pela atrofia observada em miotubos durante a inibição de Mdm2 sem a presença de T3.Previous studies in our lab through microarray assay observed Mdm2, an E3 ligase, up regulated in soleus muscle from hyperthyroid rats. In this sense, we inferred that Mdm2 could be related to muscle atrophy caused by T3. To test our hypothesis, rats were induced to experimental hyperthyroidism for subsequent analysis. Along the muscle mass loss, the increase on Mdm2 gene expression was confirmed (p<0.05) as well as protein expression by RT-PCR and Western Blot, respectively. Interestingly, Mdm2 was expressed predominantly in fiber I type during T3 treatment, demonstrating a higher sensibility when compared to type II fiber. Moreover, it was observed a severe decrease in Pax7/MyoD labeling, associated to an increase on Mdm2 labeling, suggesting that T3 could be associated with inactivation of satellite cells. Surprisingly, Mdm2 inhibition in myotubes have induced severe decrease on myotubes diameter (~35%, p<0.05), in other words, Mdm2 inhibition was not able to decrease muscle proteolysis during high levels of T3. Thus, the increase on Mdm2 levels could be a compensatory effect to reduce the muscle mass loss during T3 treatment. This conclusion is highlighted by the myotubes atrophy observed during the Mdm2 inhibition without T3 treatment

<b> The effect of stretching on muscle strength: A short review of possible causes </b>

There is currently a certain level of disagreement in the scientifi c community on the benefi ts to muscle performance of stretching before exercise. Studies researching this subject have observed a tendency for muscle strength to reduce as a result of acute stretching. Nevertheless, there are differences in the conclusions that these studies have drawn as to what are the true reasons for this loss in muscular erformance after stretching. The objective of this study, therefore, is to perform a review of literature indexed in PUBMED and SCIELO, of Brazilian and international periodicals and of textbooks on neuromuscular physiology in order to analyze the effect of stretching on muscle strength and the possible causes for this effect. After analyzing the relevant literature, it was be concluded that muscle stretching can indeed result in reduced muscle strength performance in individuals exercising to gain muscle strength, but that the causes of this process are still the subject of disagreement and that further studies are needed to better elucidate the issue. <p><b>RESUMO </b> Atualmente, o alongamento muscular antes do exercício vem trazendo controvérsias no âmbito científi co, em relação aos seus benefícios, no que diz respeito ao desempenho muscular do indivíduo. Nesta linha de pesquisa, os estudos têm observado uma tendência na diminuição da força muscular como conseqüência do alongamento agudo. Contudo, existe divergências entre os estudos sobre os motivos reais da perda de performance muscular após alongamento. Assim, o objetivo do presente estudo foi analisar, através de uma revisão de literatura nas bases de dados PUBMED, SCIELO, periódicos nacionais e internacionais assim como em livros relacionados à fi siologia neuromuscular a infl uência do alongamento sobre a força muscular e suas possíveis causas. Após a análise da literatura levantada, pode-se concluir que o alongamento muscular pode acarretar défi cit de força muscular do indivíduo, no pré-exercício para ganho de força do músculo, mas as causas para tal processo ainda são controvérsas necessitando de maiores estudos para uma melhor definição

Moderate treadmill training induces limited effects on quadriceps muscle hypertrophy in mice exposed to cigarette smoke involving metalloproteinase 2

Background: Long-term cigarette smoke (CS) induces substantive extrapulmonary effects, including musculoskeletal system disorders. Exercise training seems to protect long-term smokers against fiber atrophy in the locomotor muscles. Nevertheless, the extracellular matrix (ECM) changes in response to aerobic training remain largely unknown. Thus, we investigated the effects of moderate treadmill training on aerobic performance, crosssectional area (CSA), fiber distribution, and metalloproteinase 2 (MMP-2) activity on quadriceps muscle in mice exposed to chronic CS. Methods: Male mice were randomized into four groups: control or smoke (6 per group) and exercise or exercise+smoke (5 per group). Animals were exposed to 12 commercially filtered cigarettes per day (0.8 mg of nicotine, 10 mg of tar, and 10 mg of CO per cigarette). The CSA, fibers distribution, and MMP-2 activity by zymography were assessed after a period of treadmill training (50% of maximal exercise capacity for 60 min/day, 5 days/week) for 24 weeks. Results: The CS exposure did not change CSA compared to the control group (p>0.05), but minor fibers in the frequency distribution (<1000 µm2 ) were observed. Long-term CS exposure attenuated CSA increases in exercise conditions (smoke+exercise vs exercise) while did not impair aerobic performance. Quadriceps CSA increased in mice nonsmoker submitted to aerobic training (p = 0.001). There was higher pro-MMP-2 activity in the smoke +exercise group when compared to the smoke group (p = 0.01). Regarding active MMP-2, the exercise showed higher values when compared to the control group (p = 0.001). Conclusion: Moderate treadmill training for 24 weeks in mice exposed to CS did not modify CSA, despite inducing higher pro-MMP-2 activity in the quadriceps muscle, suggesting limited effects on ECM remodeling. Our findings may contribute to new insights into molecular mechanisms for CS conditions

Muscle IGF-1-Induced Skeletal Muscle Hypertrophy Evokes Higher Insulin Sensitivity and Carbohydrate Use as Preferential Energy Substrate

We characterized the metabolic profile of transgenic mice exhibiting enhanced muscle mass driven by increased mIGF-1 expression (MLC/mIGF-1). As expected, 6-month-old MLC/mIGF-1 mice were heavier than age-matched wild type (WT) mice (37.4 ± 0.3 versus 31.8 ± 0.6 g, resp.). MLC/mIGF-1 mice had higher respiratory quotient when compared to WT (0.9 ± 0.03 versus 0.74 ± 0.02, resp.) suggesting a preference for carbohydrate as the major fuel source. MLC/mIGF-1 mice had a higher rate of glucose disposal when compared to WT (3.25 ± 0.14 versus 2.39 ± 0.03%/min, resp.). The higher disposal rate correlated to ∼ 2-fold higher GLUT4 content in the extensor digitorum longus (EDL) muscle. Analysis of mRNA content for the glycolysis-related gene PFK-1 showed ∼ 3-fold upregulation in MLC/mIGF-1 animals. We also found a 50% downregulation of PGC1α mRNA levels in MLC/mIGF-1 mouse EDL muscle, suggesting less abundant mitochondria in this tissue. We found no difference in the expression of PPARα and PPARβ/δ, suggesting no modulation of key elements in oxidative metabolism. These data together suggest a shift in metabolism towards higher carbohydrate utilization, and that could explain the increased insulin sensitivity of hypertrophied skeletal muscle in MLC/mIGF-1 mice

Muscle IGF-1-Induced Skeletal Muscle Hypertrophy Evokes Higher Insulin Sensitivity and Carbohydrate Use as Preferential Energy Substrate

We characterized the metabolic profile of transgenic mice exhibiting enhanced muscle mass driven by increased mIGF-1 expression (MLC/mIGF-1). As expected, 6-month-old MLC/mIGF-1 mice were heavier than age-matched wild type (WT) mice (37.4 ± 0.3 versus 31.8 ± 0.6 g, resp.). MLC/mIGF-1 mice had higher respiratory quotient when compared to WT (0.9 ± 0.03 versus 0.74 ± 0.02, resp.) suggesting a preference for carbohydrate as the major fuel source. MLC/mIGF-1 mice had a higher rate of glucose disposal when compared to WT (3.25 ± 0.14 versus 2.39 ± 0.03%/min, resp.). The higher disposal rate correlated to ∼2-fold higher GLUT4 content in the extensor digitorum longus (EDL) muscle. Analysis of mRNA content for the glycolysis-related gene PFK-1 showed ∼3-fold upregulation in MLC/mIGF-1 animals. We also found a 50% downregulation of PGC1 mRNA levels in MLC/mIGF-1 mouse EDL muscle, suggesting less abundant mitochondria in this tissue. We found no difference in the expression of PPAR and PPAR / , suggesting no modulation of key elements in oxidative metabolism. These data together suggest a shift in metabolism towards higher carbohydrate utilization, and that could explain the increased insulin sensitivity of hypertrophied skeletal muscle in MLC/mIGF-1 mice

Paternal resistance exercise modulates skeletal muscle remodeling pathways in fathers and male offspring submitted to a high-fat diet

Although some studies have shown that a high-fat diet (HFD) adversely affects muscle extracellular matrix remodeling, the mechanisms involved in muscle trophism, inflammation, and adipogenesis have not been fully investigated. Thus, we investigated the effects of 8 weeks of paternal resistance training (RT) on gene and protein expression/activity of critical factors involved in muscle inflammation and remodeling of fathers and offspring (offspring exposed to standard chow or HFD). Animals were randomly distributed to constitute sedentary fathers (SF; n = 7; did not perform RT) or trained fathers (TF n = 7; performed RT), with offspring from mating with sedentary females. After birth, 28 male pups were divided into four groups (n = 7 per group): offspring from sedentary father submitted either to control diet (SFO-C) or high-fat diet (SFO-HF) and offspring from trained father submitted to control diet (TFO-C) or high-fat diet (TFO-HF). Our results show that an HFD downregulated collagen mRNA levels and upregulated inflammatory and atrophy pathways and adipogenic transcription factor mRNA levels in offspring gastrocnemius muscle. In contrast, paternal RT increased MMP-2 activity and decreased IL-6 levels in offspring exposed to a control diet. Paternal RT upregulated P70s6k and Ppara mRNA levels and downregulated Atrogin1 mRNA levels, while decreasing NFκ-B, IL-1β, and IL-8 protein levels in offspring exposed to an HFD. Paternal physical training influences key skeletal muscle remodeling pathways and inflammatory profiles relevant for muscle homeostasis maintenance in offspring submitted to different diets

Effect of photobiomodulation and exercise on early remodeling of the Achilles tendon in streptozotocin-induced diabetic rats.

The aim of this study was to compare the treatment effects of laser photobiomodulation (LPBM) therapy and aerobic exercise on the biomechanical properties, tissue morphology and the expression of tendon matrix molecules during early remodeling of Achilles tendon (AT) injury in diabetic rats. Animals were randomly assigned to five groups: injured non diabetic (I, n = 15), injured diabetic (ID, n = 15), injured diabetic plus LPBM (IDL, n = 16), injured diabetic plus aerobic exercise (IDE, n = 16) and injured diabetic plus aerobic exercise and LPBM (IDEAL, n = 17). Type 1 diabetes was induced via a single intravenous injection of Streptozotocin at a dose of 40 mg/kg. A partial tenotomy was performed in the right AT. LPBM was performed with an indium-gallium-aluminum-phosphide 660 nm 10 mW laser device (spot size 0.04 cm2, power density 250 mW/cm2, irradiation duration 16 s, energy 0.16 J, energy density 4 J/cm2) on alternate days for a total of 9 sessions over 3 weeks (total energy 1.44 J), using a stationary contact technique to a single point over the dorsal aspect of the AT. Moderate aerobic exercise was performed on a motorized treadmill (velocity 9 m/min for 60 minutes). At 3 weeks post-injury, biomechanical analyzes as well as assessment of fibroblast number and orientation were performed. Collagen 1 (Col1) and 3 (Col3) and matrix metalloproteinases (MMPs) -3 and 13 protein distributions were studied by immunohistochemistry; while Col1 and Col3 and MMP-2 and 9 gene expression were assessed by quantitative RT-PCR (qRT-PCR). IDEAL exhibited significant increases in several biomechanical parameters in comparison to the other groups. Moreover, IDEAL presented stronger Col1 immunoreactivity when compared to ID, and weaker Col3 immunoreactivity than IDE. Both IDL and IDEAL demonstrated weaker expression of MMP-3 in comparison to I, while IDL presented no expression of MMP-13 when compared to ID. ID, IDL and IDE showed an increased number of fibroblasts in comparison to I, while IDEAL decreased the number of these cells in comparison to ID and IDE. IDL and IDEAL groups exhibited decreased angular dispersion among the fibroblasts when compared to I. The gene expression results showed that IDE demonstrated a downregulation in Col1 mRNA expression in comparison to I and ID. IDEAL demonstrated upregulation of Col1 mRNA expression when compared to IDL or IDE alone and increased MMP-2 expression when compared to IDL and IDE. MMP-9 expression was upregulated in IDEAL when compared to I, IDL and IDE. Our results suggest a beneficial interaction of combining both treatment strategies i.e., aerobic exercise and LPBM, on the biomechanical properties, tissue morphology and the expression of matrix molecules in diabetic tendons