Myostatin: more than just a regulator of muscle mass

Definition and classification of cancer cachexia: an international consensus

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Regulation of skeletal muscle mass in mice by a new TGF-p superfamily member

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Cachexia: a new definition.

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Myostatin, a Negative Regulator of Muscle Growth, Functions by Inhibiting Myoblast Proliferation

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Reversal of Cancer Cachexia and Muscle Wasting by ActRIIB Antagonism Leads to Prolonged Survival

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Myostatin Inhibits Myoblast Differentiation by Down-regulating MyoD Expression

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Induction of Cachexia in Mice by Systemically Administered Myostatin

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Functional improvement of dystrophic muscle by myostatin blockade

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REGULATION OF MUSCLE MASS BY MYOSTATIN

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Adipose Triglyceride Lipase Contributes to Cancer-Associated Cachexia

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Organization of the human myostatin gene and expression in healthy men and HIV-infected men with muscle wasting

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Inhibition of myostatin in adult mice increases skeletal muscle mass and strength

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Suppression of body fat accumulation in myostatin-deficient mice

McPherron, A. C., & Lee, S.-J. (2002) · Journal of Clinical Investigation · doi:10.1172/jci0213562 · Cited by 505

Myostatin induces cachexia by activating the ubiquitin proteolytic system through an NF‐κB‐independent, FoxO1‐dependent mechanism

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The transforming growth factor-β superfamily of receptors

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Activation of latent myostatin by the BMP-1/tolloid family of metalloproteinases

Wolfman, N. M., McPherron, A. C., Pappano, W. N., Davies, M. V., Song, K., Tomkinson, K. N., Wright, J. F., Zhao, L., Sebald, S. M., Greenspan, D. S., et al. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2534946100 · Cited by 454

The Myostatin Propeptide and the Follistatin-related Gene Are Inhibitory Binding Proteins of Myostatin in Normal Serum

Hill, J. J., Davies, M. V., Pearson, A. A., Wang, J. H., Hewick, R. M., Wolfman, N. M., & Qiu, Y. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m206379200 · Cited by 444

Lack of myostatin results in excessive muscle growth but impaired force generation

Amthor, H., Macharia, R., Navarrete, R., Schuelke, M., Brown, S., Otto, A., Voït, T., Muntoni, F., Vrbovà, G., Partridge, T. A., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0604893104 · Cited by 438

Myostatin inhibits cell proliferation and protein synthesis in C2C12 muscle cells

Taylor, W. E., Bhasin, S., Artaza, J., Byhower, F., Azam, M., Willard, D. H., Kull, F. C., & González-Cadavid, N. F. (2001) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.2001.280.2.e221 · Cited by 410

Myostatin inhibition in muscle, but not adipose tissue, decreases fat mass and improves insulin sensitivity

Guo, T., Jou, W., Chanturiya, T., Portas, J., Gavrilova, O., & McPherron, A. C. (2009) · PLoS ONE · doi:10.1371/journal.pone.0004937 · Cited by 402

Signaling pathways perturbing muscle mass.

Glass, D. J. (2010) · Current Opinion in Clinical Nutrition and Metabolic Care · doi:10.1097/mco.0b013e32833862df · Cited by 359

Functional and morphological recovery of dystrophic muscles in mice treated with deacetylase inhibitors

Minetti, G., Colussi, C., Adami, R., Serra, C., Mozzetta, C., Parente, V., Fortuni, S., Straino, S., Sampaolesi, M., Padova, M. D., et al. (2006) · Nature Medicine · doi:10.1038/nm1479 · Cited by 343

Increased secretion and expression of myostatin in skeletal muscle from extremely obese women

Hittel, D. S., Berggren, J. R., Shearer, J., Boyle, K., & Houmard, J. A. (2009) · Diabetes · doi:10.2337/db08-0943 · Cited by 324

Serum myostatin-immunoreactive protein is increased in 60-92 year old women and men with muscle wasting.

Yarasheski, K. E., Bhasin, S., Sinha‐Hikim, I., Pak-Loduca, J., & González-Cadavid, N. F. (2002) · PubMed · Cited by 293

Human Sarcopenia Reveals an Increase in SOCS-3 and Myostatin and a Reduced Efficiency of Akt Phosphorylation

Léger, B., Derave, W., Bock, K. D., Hespel, P., & Russell, A. P. (2008) · Rejuvenation Research · doi:10.1089/rej.2007.0588 · Cited by 285

Myostatin and the control of skeletal muscle mass

Lee, S., & McPherron, A. C. (1999) · Current Opinion in Genetics & Development · doi:10.1016/s0959-437x(99)00004-0 · Cited by 274

Myostatin decreases with aerobic exercise and associates with insulin resistance

HITTEL, D. S., AXELSON, M., SARNA, N., SHEARER, J., HUFFMAN, K. M., & KRAUS, W. E. (2010) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0b013e3181e0b9a8 · Cited by 271

Structure of the ternary signaling complex of a TGF-β superfamily member

Allendorph, G. P., Vale, W., & Choe, S. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0602558103 · Cited by 251

Deacetylase Inhibitors Increase Muscle Cell Size by Promoting Myoblast Recruitment and Fusion through Induction of Follistatin

Iezzi, S., Padova, M. D., Serra, C., Caretti, G., Simone, C., Maklan, E., Minetti, G., Zhao, P., Hoffman, E. P., Puri, P., et al. (2004) · Developmental Cell · doi:10.1016/s1534-5807(04)00107-8 · Cited by 245

Genetic deletion of myostatin from the heart prevents skeletal muscle atrophy in heart failure

Heineke, J., Auger-Messier, M., Xu, J., Sargent, M., York, A., Welle, S., & Molkentin, J. D. (2010) · Circulation · doi:10.1161/circulationaha.109.882068 · Cited by 238

Acute inhibition of myostatin-family proteins preserves skeletal muscle in mouse models of cancer cachexia

Klimek, M. B., Aydogdu, T., Link, M., Pons, M., Koniaris, L. G., & Zimmers, T. A. (2009) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2009.12.123 · Cited by 229

Secreted proteins from adipose tissue and skeletal muscle – adipokines, myokines and adipose/muscle cross-talk

Trayhurn, P., Drevon, C. A., & Eckel, J. (2011) · Archives of Physiology and Biochemistry · doi:10.3109/13813455.2010.535835 · Cited by 214

The role of cytokines in cancer cachexia

Argilés, J. M. A., Busquets, S., Toledo, M., & López-Soriano, F. J. (2009) · Current Opinion in Supportive and Palliative Care · doi:10.1097/spc.0b013e3283311d09 · Cited by 212

Myostatin modulates adipogenesis to generate adipocytes with favorable metabolic effects

Feldman, B. J., Streeper, R. S., Farese, R. V., & Yamamoto, K. R. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0607501103 · Cited by 211

Myostatin Inhibits Myogenesis and Promotes Adipogenesis in C3H 10T(1/2) Mesenchymal Multipotent Cells

Artaza, J. N., Bhasin, S., Magee, T. R., Reisz‐Porszasz, S., Shen, R., Groome, N. P., Fareez, M. M., & González-Cadavid, N. F. (2005) · Endocrinology · doi:10.1210/en.2005-0362 · Cited by 206

Myostatin (GDF-8) as a key factor linking muscle mass and bone structure.

Elkasrawy, M., & Hamrick, M. W. (2010) · PubMed · Cited by 201

Exercise induces a marked increase in plasma follistatin: Evidence that follistatin is a contraction-induced hepatokine

Hansen, J., Brandt, C., Nielsen, A. R., Hojman, P., Whitham, M., Febbraio, M. A., Pedersen, B. K., & Plomgaard, P. (2011) · Endocrinology · doi:10.1210/en.2010-0868 · Cited by 200

Inhibition of myostatin with emphasis on follistatin as a therapy for muscle disease

Rodino‐Klapac, L. R., Haidet, A. M., Kota, J., Handy, C., Kaspar, B. K., & Mendell, J. R. (2009) · Muscle & Nerve · doi:10.1002/mus.21244 · Cited by 194

Cross-talk between skeletal muscle and adipose tissue: A link with obesity?

Argilés, J. M. A., López‐Soriano, J., Almendro, V., Busquets, S., & López-Soriano, F. J. (2004) · Medicinal Research Reviews · doi:10.1002/med.20010 · Cited by 194

Inhibition of myostatin protects against diet-induced obesity by enhancing fatty acid oxidation and promoting a brown adipose phenotype in mice

Zhang, C., McFarlane, C., Lokireddy, S., Masuda, S., Ge, X., Gluckman, P. D., Sharma, M., & Kambadur, R. (2012) · Diabetologia · doi:10.1007/s00125-011-2304-4 · Cited by 192

Transgenic expression of myostatin propeptide prevents diet-induced obesity and insulin resistance

Zhao, B., Wall, R. J., & Yang, J. (2005) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2005.09.044 · Cited by 186

Muscle myostatin signalling is enhanced in experimental cancer cachexia

Costelli, P., Muscaritoli, M., Bonetto, A., Penna, F., Reffo, P., Bossola, M., Bonelli, G., Doglietto, G. B., Baccino, F. M., & Fanelli, F. R. (2008) · European Journal of Clinical Investigation · doi:10.1111/j.1365-2362.2008.01970.x · Cited by 186

TNF Can Directly Induce the Expression of Ubiquitin-Dependent Proteolytic System in Rat Soleus Muscles

Llovera, M., Garcia‐Martínez, C., Agell, N., López-Soriano, F. J., & Argilés, J. M. A. (1997) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1996.5827 · Cited by 184

Myostatin, activin receptor IIb, and follistatin-like-3 gene expression are altered in adipose tissue and skeletal muscle of obese mice

Allen, D. L., Cleary, A. S., Speaker, K. J., Lindsay, S. F., Uyenishi, J., Reed, J. M., Madden, M. C., & Mehan, R. S. (2008) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00798.2007 · Cited by 183

Anticachectic Effects of Formoterol

Busquets, S., Figueras, M. T., Fuster, G., Almendro, V., Moore‐Carrasco, R., Ametller, E., Argilés, J. M. A., & López-Soriano, F. J. (2004) · Cancer Research · doi:10.1158/0008-5472.can-04-0425 · Cited by 167

Increased muscle ubiquitin mRNA levels in gastric cancer patients.

Bossola, M., Muscaritoli, M., Costelli, P., Bellantone, R., Pacelli, F., Busquets, S., Argilès, J., López-Soriano, F., Civello, I. M., Baccino, F., et al. (2001) · American Journal of Physiology. Regulatory Integrative and Comparative Physiology · doi:10.1152/ajpregu.2001.280.5.r1518 · Cited by 164

Ectopic Expression of Myostatin Induces Atrophy of Adult Skeletal Muscle by Decreasing Muscle Gene Expression

Durieux, A., Amirouche, A., Banzet, S., Koulmann, N., Bonnefoy, R., Pasdeloup, M., Mouret, C., Bigard, X. A., Peinnequin, A., & Freyssenet, D. G. (2007) · Endocrinology · doi:10.1210/en.2006-1500 · Cited by 162

The myostatin gene: physiology and pharmacological relevance

Joulia-Ekaza, D., & Cabello, G. (2007) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2006.11.011 · Cited by 162

Myostatin Propeptide Gene Delivery by Adeno-Associated Virus Serotype 8 Vectors Enhances Muscle Growth and Ameliorates Dystrophic Phenotypes in mdx Mice

Qiao, C., Li, J., Jiang, J., Zhu, X., Wang, B., Li, J., & Xiao, X. (2008) · Human Gene Therapy · doi:10.1089/hum.2007.159 · Cited by 161

Identification of a Novel Pool of Extracellular Pro-myostatin in Skeletal Muscle

Anderson, S. B., Goldberg, A. L., & Whitman, M. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m706678200 · Cited by 159

Myostatin-deficient mice exhibit reduced insulin resistance through activating the AMP-activated protein kinase signalling pathway

Zhang, C., McFarlane, C., Lokireddy, S., Bonala, S., Ge, X., Masuda, S., Gluckman, P. D., Sharma, M., & Kambadur, R. (2011) · Diabetologia · doi:10.1007/s00125-011-2079-7 · Cited by 158

The effects of a soluble activin type IIB receptor on obesity and insulin sensitivity

Akpan, I., Goncalves, M. D., Dhir, R., Yin, X., Pistilli, E. E., Bogdanovich, S., Khurana, T. S., Ucran, J., Lachey, J., & Ahima, R. S. (2009) · International Journal of Obesity · doi:10.1038/ijo.2009.162 · Cited by 140

Exercise training leads to a reduction of elevated myostatin levels in patients with chronic heart failure

Lenk, K., Erbs, S., Höllriegel, R., Beck, E. B., Linke, A. H.-P., Gielen, S., Winkler, S. M., Sandri, M., Hambrecht, R., Schuler, G. C., et al. (2011) · European Journal of Preventive Cardiology · doi:10.1177/1741826711402735 · Cited by 140

Prolonged absence of myostatin reduces sarcopenia

Siriett, V., Platt, L., Salerno, M. S., Ling, N., Kambadur, R., & Sharma, M. (2006) · Journal of Cellular Physiology · doi:10.1002/jcp.20778 · Cited by 139

Myostatin from the heart: local and systemic actions in cardiac failure and muscle wasting

Breitbart, A., Auger‐Messier, M., Molkentin, J. D., & Heineke, J. (2011) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00200.2011 · Cited by 139

The Regulation and Action of Myostatin as a Negative Regulator of Muscle Development during Avian Embryogenesis

Amthor, H., Huang, R., McKinnell, I. W., Christ, B., Kambadur, R., Sharma, M., & Patel, K. (2002) · Developmental Biology · doi:10.1006/dbio.2002.0812 · Cited by 138

Impact of Exercise Training on Myostatin Expression in the Myocardium and Skeletal Muscle in a Chronic Heart Failure Model

Lenk, K., Schur, R., Linke, A., Erbs, S., Matsumoto, Y., Adams, V., & Schuler, G. C. (2009) · European Journal of Heart Failure · doi:10.1093/eurjhf/hfp020 · Cited by 136

Skeletal Muscle Hypertrophy and Muscle Myostatin Reduction After Resistive Training in Stroke Survivors

Ryan, A. S., Ivey, F. M., Prior, S. J., Li, G., & Hafer‐Macko, C. E. (2010) · Stroke · doi:10.1161/strokeaha.110.602441 · Cited by 134

Transcriptional profiling of myostatin‐knockout mice implicates Wnt signaling in postnatal skeletal muscle growth and hypertrophy

Steelman, C. A., Recknor, J. C., Nettleton, D. S., & Reecy, J. M. (2006) · The FASEB Journal · doi:10.1096/fj.05-5125fje · Cited by 133

Recent advances in the biology and therapy of muscle wasting

Glass, D. J., & Roubenoff, R. (2010) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2010.05809.x · Cited by 130

Decorin enhances the proliferation and differentiation of myogenic cells through suppressing myostatin activity

Kishioka, Y., Thomas, M., Wakamatsu, J., Hattori, A., Sharma, M., Kambadur, R., & Nishimura, T. (2007) · Journal of Cellular Physiology · doi:10.1002/jcp.21371 · Cited by 130

Antibody‐directed myostatin inhibition in 21‐mo‐old mice reveals novel roles for myostatin signaling in skeletal muscle structure and function

Murphy, K. T., Koopman, R., Naim, T., Léger, B., Trieu, J., Ibebunjo, C., & Lynch, G. S. (2010) · The FASEB Journal · doi:10.1096/fj.10-159608 · Cited by 129

Muscular atrophy of caveolin-3–deficient mice is rescued by myostatin inhibition

Ohsawa, Y., Hagiwara, H., Nakatani, M., Yasue, A., Moriyama, K., Murakami, T., Tsuchida, K., Noji, S., & Sunada, Y. (2006) · Journal of Clinical Investigation · doi:10.1172/jci28520 · Cited by 122

Genetic Analysis of the Role of Proteolysis in the Activation of Latent Myostatin

Lee, S.-J. (2008) · PLoS ONE · doi:10.1371/journal.pone.0001628 · Cited by 114

Structure to function: muscle failure in critically ill patients

Puthucheary, Z., Montgomery, H., Moxham, J., Harridge, S. D. R., & Hart, N. (2010) · The Journal of Physiology · doi:10.1113/jphysiol.2010.197632 · Cited by 106

Regulation of myostatin signaling by c-Jun N-terminal kinase in C2C12 cells

Huang, Z., Chen, D., Zhang, K., Yu, B., Chen, X., & Meng, J. (2007) · Cellular Signalling · doi:10.1016/j.cellsig.2007.07.002 · Cited by 104

Changes in Muscle Myostatin Expression in Obese Subjects after Weight Loss

Milan, G., Nora, E. D., Pilon, C., Pagano, C., Granzotto, M., Manco, M., Mingrone, G., & Vettor, R. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-032047 · Cited by 100

Myostatin antisense RNA-mediated muscle growth in normal and cancer cachexia mice

Cm, L., Yang, Z., Liu, C.-W., Wang, R., Tien, P., Dale, R., & Sun, L.-Q. (2007) · Gene Therapy · doi:10.1038/sj.gt.3303016 · Cited by 100

Myostatin Up-Regulation Is Associated with the Skeletal Muscle Response to Hypoxic Stimuli

Hayot, M., Rodriguez, J., Vernus, B., Carnac, G., Jean, E., Allen, D., Goret, L., Obert, P., Candau, R., & Bonnieu, A. (2011) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2010.09.008 · Cited by 98

Systemic inflammation correlates with increased expression of skeletal muscle ubiquitin but not uncoupling proteins in cancer cachexia

Dejong, C. H. C., Busquets, S., Moses, A. G. W., Schrauwen, P., Ross, J. A., Argilés, J. M. A., & Fearon, K. C. H. (2005) · Oncology Reports · doi:10.3892/or.14.1.257 · Cited by 90

Atrophy and hypertrophy signalling in the diaphragm of patients with COPD

Testelmans, D., Crul, T., Maes, K., Agten, A., Crombach, M., Decramer, M., & Gayan‐Ramirez, G. (2009) · European Respiratory Journal · doi:10.1183/09031936.00091108 · Cited by 87

Changes in Myostatin Signaling in Non-Weight-Losing Cancer Patients

Aversa, Z., Bonetto, A., Penna, F., Costelli, P., Rienzo, G. D., Lacitignola, A., Baccino, F. M., Ziparo, V., Mercantini, P., Fanelli, F. R., et al. (2011) · Annals of Surgical Oncology · doi:10.1245/s10434-011-1720-5 · Cited by 85

Targeting myostatin for therapies against muscle-wasting disorders.

Tsuchida, K. (2008) · PubMed · Cited by 84

Myostatin in Muscle Growth and Repair

Sharma, M., Langley, B. C., Bass, J. J., & Kambadur, R. (2001) · Exercise and Sport Sciences Reviews · doi:10.1097/00003677-200110000-00004 · Cited by 84

Effect of RNA oligonucleotide targeting Foxo-1 on muscle growth in normal and cancer cachexia mice

Cm, L., Yang, Z., Liu, C.-W., Wang, R., Tien, P., Dale, R., & Sun, L.-Q. (2007) · Cancer Gene Therapy · doi:10.1038/sj.cgt.7701091 · Cited by 83

Combination of Myostatin Pathway Interference and Dystrophin Rescue Enhances Tetanic and Specific Force in Dystrophic mdx Mice

Dumonceaux, J., Marie, S., Beley, C., Trollet, C., Vignaud, A., Ferry, A., Butler-Browne, G. S., & Garcı́a, L. (2010) · Molecular Therapy · doi:10.1038/mt.2009.322 · Cited by 81

Myostatin blockade improves function but not histopathology in a murine model of limb‐girdle muscular dystrophy 2C

Bogdanovich, S., McNally, E. M., & Khurana, T. S. (2007) · Muscle & Nerve · doi:10.1002/mus.20920 · Cited by 77

Deacetylase Inhibitors Modulate the Myostatin/Follistatin Axis without Improving Cachexia in Tumor-Bearing Mice

Bonetto, A., Penna, F., Minero, V. G., Reffo, P., Bonelli, G., Baccino, F. M., & Costelli, P. (2009) · Current Cancer Drug Targets · doi:10.2174/156800909789057015 · Cited by 72

The Effect of Glutamine on Prevention of Glucocorticoid-Induced Skeletal Muscle Atrophy Is Associated with Myostatin Suppression

Salehian, B., Mahabadi, V., Bilas, J., Taylor, W. E., & Ma, K. (2006) · Metabolism · doi:10.1016/j.metabol.2006.05.009 · Cited by 69

Upregulation of myostatin gene expression in streptozotocin-induced type 1 diabetes mice is attenuated by insulin

Chen, Y., Cao, L., Ye, J., & Zhu, D. (2009) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2009.07.129 · Cited by 64

Systemic Myostatin Inhibition via Liver-Targeted Gene Transfer in Normal and Dystrophic Mice

Morine, K., Bish, L. T., Pendrak, K., Sleeper, M. M., Barton, E. R., & Sweeney, H. L. (2010) · PLoS ONE · doi:10.1371/journal.pone.0009176 · Cited by 63

Role of Follistatin in Promoting Adipogenesis in Women

Flanagan, J. N., Linder, K., Mejhert, N., Dungner, E., Wåhlén, K., Decaunes, P., Rydén, M., Björklund, P., Arver, S., Bhasin, S., et al. (2009) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2008-2005 · Cited by 63

Sprinting without myostatin: a genetic determinant of athletic prowess

Lee, S. (2007) · Trends in Genetics · doi:10.1016/j.tig.2007.08.008 · Cited by 62

Mechanisms to explain wasting of muscle and fat in cancer cachexia

Argilés, J. M. A., López-Soriano, F. J., & Busquets, S. (2007) · Current Opinion in Supportive and Palliative Care · doi:10.1097/spc.0b013e3282f34738 · Cited by 58

Inhibiting Myostatin with Follistatin Improves the Success of Myoblast Transplantation in Dystrophic Mice

Benabdallah, B., Bouchentouf, M., Rousseau, J., Bigey, P., Michaud, A., Chapdelaine, P., Scherman, D., & Tremblay, J. P. (2008) · Cell Transplantation · doi:10.3727/096368908784153913 · Cited by 53

Quadriceps Myostatin Expression in COPD

D-C. Man, W., Natanek, S. A., Riddoch-Contreras, J., Lewis, A., Marsh, G. S., Kemp, P. R., & Polkey, M. I. (2010) · European Respiratory Journal · doi:10.1183/09031936.00032510 · Cited by 48

Myostatin regulates preadipocyte differentiation and lipid metabolism of adipocyte via ERK1/2

Li, F., Yang, H., Duan, Y., & Yin, Y. (2011) · Cell Biology International · doi:10.1042/cbi20110112 · Cited by 47

Glutamine prevents myostatin hyperexpression and protein hypercatabolism induced in C2C12 myotubes by tumor necrosis factor-α

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Blocking the Myostatin Signal With a Dominant Negative Receptor Improves the Success of Human Myoblast Transplantation in Dystrophic Mice

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