scholarly journals Mesenchymal Stem Cell-Derived Exosomes Protect Muscle Loss by miR-145-5p Activity Targeting Activin A Receptors

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 2169
Author(s):  
Kyung-Ah Cho ◽  
Da-Won Choi ◽  
Yu-Hee Kim ◽  
Jungwoo Kim ◽  
Kyung-Ha Ryu ◽  
...  

Skeletal muscle mass is decreased under a wide range of pathologic conditions. In particular, chemotherapy is well known for inducing muscle loss and atrophy. Previous studies using tonsil-derived mesenchymal stem cells (T-MSCs) or a T-MSC-conditioned medium showed effective recovery of total body weight in the chemotherapy-preconditioned bone marrow transplantation mouse model. This study investigated whether extracellular vesicles of T-MSCs, such as exosomes, are a key player in the recovery of body weight and skeletal muscle mass in chemotherapy-treated mice. T-MSC exosomes transplantation significantly decreased loss of total body weight and muscle mass in the busulfan-cyclophosphamide conditioning regimen in BALB/c recipient mice containing elevated serum activin A. Additionally, T-MSC exosomes rescued impaired C2C12 cell differentiation in the presence of activin A in vitro. We found that T-MSC exosomes possess abundant miR-145-5p, which targets activin A receptors, ACVR2A, and ACVR1B. Indeed, T-MSC exosomes rescue muscle atrophy both in vivo and in vitro via miR-145-5p dependent manner. These results suggest that T-MSC exosomes have therapeutic potential to maintain or improve skeletal muscle mass in various activin A elevated pathologic conditions.

2000 ◽  
Vol 279 (2) ◽  
pp. E366-E375 ◽  
Author(s):  
Dympna Gallagher ◽  
Else Ruts ◽  
Marjolein Visser ◽  
Stanley Heshka ◽  
Richard N. Baumgartner ◽  
...  

Skeletal muscle loss or sarcopenia in aging has been suggested in cross-sectional studies but has not been shown in elderly subjects using appropriate measurement techniques combined with a longitudinal study design. Longitudinal skeletal muscle mass changes after age 60 yr were investigated in independently living, healthy men ( n = 24) and women ( n = 54; mean age 73 yr) with a mean ± SD follow-up time of 4.7 ± 2.3 yr. Measurements included regional skeletal muscle mass, four additional lean components (fat-free body mass, body cell mass, total body water, and bone mineral), and total body fat. Total appendicular skeletal muscle (TSM) mass decreased in men (−0.8 ± 1.2 kg, P = 0.002), consisting of leg skeletal muscle (LSM) loss (−0.7 ± 0.8 kg, P = 0.001) and a trend toward loss of arm skeletal muscle (ASM; −0.2 ± 0.4 kg, P = 0.06). In women, TSM mass decreased (−0.4 ± 1.2 kg, P = 0.006) and consisted of LSM loss (−0.3 ± 0.8 kg, P = 0.005) and a tendency for a loss of ASM (−0.1 ± 0.6 kg, P = 0.20). Multiple regression modeling indicates greater rates of LSM loss in men. Body weight in men at follow-up did not change significantly (−0.5 ± 3.0 kg, P = 0.44) and fat mass increased (+1.2 ± 2.4 kg, P = 0.03). Body weight and fat mass in women were nonsignificantly reduced (−0.8 ± 3.9 kg, P= 0.15 and −0.8 ± 3.5 kg, P = 0.12). These observations suggest that sarcopenia is a progressive process, particularly in elderly men, and occurs even in healthy independently living older adults who may not manifest weight loss.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Tomoaki Takata ◽  
Yukari Mae ◽  
Kentaro Yamada ◽  
Sosuke Taniguchi ◽  
Shintaro Hamada ◽  
...  

Abstract Background Hyporesponsiveness to erythropoietin stimulating agent (ESA) is associated with poor outcomes in patients with chronic kidney disease. Although ESA hyporesponsiveness and sarcopenia have a common pathophysiological background, clinical evidence linking them is scarce. The purpose of the study was to investigate the relationship between ESA responsiveness and skeletal muscle mass in hemodialysis patients. Methods This cross-sectional study analyzed 70 patients on maintenance hemodialysis who were treated with ESA. ESA responsiveness was evaluated by erythropoietin resistance index (ERI), calculated as a weekly dose of ESA divided by body weight and hemoglobin (IU/kg/week/dL), and a weekly dose of ESA/hemoglobin (IU/week/dL). A dose of ESA is equivalated to epoetin β. Correlations between ESA responsiveness and clinical parameters including skeletal muscle mass were analyzed. Results Among the 70 patients, ERI was positively correlated to age (p < 0.002) and negatively correlated to height (p < 0.001), body weight (p < 0.001), BMI (p < 0.001), skeletal muscle mass (p < 0.001), transferrin saturation (TSAT) (p = 0.049), and zinc (p = 0.006). In the multiple linear regression analysis, TSAT, zinc, and skeletal muscle mass were associated with ERI and weekly ESA dose/hemoglobin. Conclusions Skeletal muscle mass was the independent predictor for ESA responsiveness as well as TSAT and zinc. Sarcopenia is another target for the management of anemia in patients with hemodialysis.


2016 ◽  
Vol 41 (6) ◽  
pp. 611-617 ◽  
Author(s):  
Jameason D. Cameron ◽  
Ronald J. Sigal ◽  
Glen P. Kenny ◽  
Angela S. Alberga ◽  
Denis Prud’homme ◽  
...  

There has been renewed interest in examining the relationship between specific components of energy expenditure and the overall influence on energy intake (EI). The purpose of this cross-sectional analysis was to determine the strongest metabolic and anthropometric predictors of EI. It was hypothesized that resting metabolic rate (RMR) and skeletal muscle mass would be the strongest predictors of EI in a sample of overweight and obese adolescents. 304 post-pubertal adolescents (91 boys, 213 girls) aged 16.1 (±1.4) years with body mass index at or above the 95th percentile for age and sex OR at or above the 85th percentile plus an additional diabetes risk factor were measured for body weight, RMR (kcal/day) by indirect calorimetry, body composition by magnetic resonance imaging (fat free mass (FFM), skeletal muscle mass, fat mass (FM), and percentage body fat), and EI (kcal/day) using 3 day food records. Body weight, RMR, FFM, skeletal muscle mass, and FM were all significantly correlated with EI (p < 0.005). After adjusting the model for age, sex, height, and physical activity, only FFM (β = 21.9, p = 0.007) and skeletal muscle mass (β = 25.8, p = 0.02) remained as significant predictors of EI. FFM and skeletal muscle mass also predicted dietary protein and fat intake (p < 0.05), but not carbohydrate intake. In conclusion, with skeletal muscle mass being the best predictor of EI, our results support the hypothesis that the magnitude of the body’s lean tissue is related to absolute levels of EI in a sample of inactive adolescents with obesity.


2007 ◽  
Vol 137 (8) ◽  
pp. 1988-1991 ◽  
Author(s):  
ZiMian Wang ◽  
Stanley Heshka ◽  
Angelo Pietrobelli ◽  
Zhao Chen ◽  
Analiza M. Silva ◽  
...  

2019 ◽  
Vol 30 (3) ◽  
pp. 421-428
Author(s):  
Tessa E. Morris‐Paterson ◽  
Stephen A. Stimpson ◽  
Ram R. Miller ◽  
Matthew E. Barton ◽  
Michael S. Leonard ◽  
...  

2002 ◽  
Vol 76 (2) ◽  
pp. 378-383 ◽  
Author(s):  
Jaehee Kim ◽  
ZiMian Wang ◽  
Steven B Heymsfield ◽  
Richard N Baumgartner ◽  
Dympna Gallagher

2020 ◽  
Vol 67 (7) ◽  
pp. 733-740 ◽  
Author(s):  
Kensuke Nishida ◽  
Yoshitaka Hashimoto ◽  
Ayumi Kaji ◽  
Takuro Okamura ◽  
Ryousuke Sakai ◽  
...  

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15633-e15633
Author(s):  
Matthew Peloquin ◽  
Brianna LaCarubba ◽  
Stephanie Joaqium ◽  
Gregory Weber ◽  
John Stansfield ◽  
...  

e15633 Background: Almost half of cancer deaths are attributed to cancers most frequently associated with cachexia. Cachexia is a complex metabolic disease characterized by anorexia and unintentional weight loss. Skeletal muscle depletion has been recognized as a key feature of the disease, however muscle anabolic therapies have not been successful, suggesting that treatments that target multiple aspects of the disease will be most effective. Growth differentiation factor 15 (GDF-15) is a cytokine that induces anorexia and weight loss and is associated with cachexia in cancer patients. In preclinical cancer cachexia models, GDF-15 inhibition is sufficient to normalize food intake and body weight, including skeletal muscle mass. However, it remains to be determined whether the increased skeletal muscle mass also results in restoration of muscle function. Therefore, we examined the effect of GDF-15 inhibition on muscle mass and function in mouse models of cancer cachexia in comparison with myostatin inhibition, an established muscle anabolic pathway. Methods: Cachectic mouse tumor models were established with subcutaneous implantation of tumor cell lines reported to be GDF-15-dependent; mouse renal cell carcinoma (RENCA) and human ovarian cancer (TOV-21G) cell lines. Mice were treated with anti-GDF-15 (mAB2) or anti-myostatin (RK35) monoclonal antibodies and skeletal muscle function was assessed in vivo via maximum force, maximum rate of contraction and half relax time. In the RENCA tumor model, GDF-15 inhibition fully restored body weight and skeletal muscle mass whereas myostatin inhibition showed only a modest effect. Results: Consistent with the muscle mass improvement, GDF-15 inhibition dramatically increased functional muscle endpoints compared to the partial effect of myostatin inhibition. Interestingly, in the TOV-21G tumor model GDF-15 inhibition only partially restored body weight, however skeletal muscle mass and muscle function were completely normalized. Consistent with the functional assessment, GDF-15 inhibition in the RENCA tumor model decreased the expression of several catabolic genes (i.e. Trim63, Fbxo32, Myh7 and Myh2). The GDF-15 effect is likely to be secondary to the reversal of anorexia since wildtype mice pair-fed to Fc-GDF-15-treated mice demonstrated equivalent muscle mass loss. Conclusions: Taken together these data suggest that GDF-15 inhibition holds potential as an effective therapeutic approach to alleviate multiple aspects of cachexia.


2009 ◽  
Vol 28 (1) ◽  
pp. 52-58 ◽  
Author(s):  
Marja Tengvall ◽  
Lars Ellegård ◽  
Vibeke Malmros ◽  
Niklas Bosaeus ◽  
Lauren Lissner ◽  
...  

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