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The Plasticity of Skeletal Muscle -

The Plasticity of Skeletal Muscle (eBook)

From Molecular Mechanism to Clinical Applications

Kunihiro Sakuma (Herausgeber)

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2017 | 1st ed. 2017
IX, 292 Seiten
Springer Singapore (Verlag)
978-981-10-3292-9 (ISBN)
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This book discusses recent advances and various topics in plasticity of skeletal muscle from the perspectives of morphology, biological function, and clinical applications. Skeletal muscle is a highly plastic organ to adapt to environmental various demands, appears to endocrine various myokines, which flow into blood to protect the recognizing function of brain and inhibit the appearance of several cancer tumorigenesis.

The book deals with current stem-cell based, pharmacological, and nutritional therapies for muscle wasting (sarcopenia, cachexia, and muscular dystrophy). It also explains the roles of biological mediators such as PGC-1, transient receptor potential cation channels (TRPC), and AMPK in modulating muscle function. The functional roles of ubiquitin-proteasome system, autophagy-dependent signaling in muscle homeostasis, ribosome biogenesis, and redox regulation of mechanotransduction to modulate skeletal muscle mass are also covered.

It is an essential resource for physicians, researchers, post-docs as well as graduate students in the field of sports science including rehabilitation therapy, exercise physiology, exercise biochemistry, and molecular biology dealing with skeletal muscle.


Professor Kunihiro Sakuma, Ph.D., currently works at Department for Liberal Arts in Tokyo Institute of Technology. He is a Physiologist working in the field of skeletal muscle. He was awarded sports science diploma in 1995 by the University of Tsukuba and started scientific work at the Department of Physiology, Aichi Human Science Center, focusing on the molecular mechanism of congenital muscular dystrophy and normal muscle regeneration. His interest later was turned to the molecular mechanism and the attenuating strategy of sarcopenia (age-related muscle atrophy). Preventing sarcopenia is important for maintaining a high quality of life in the aged population. His opinion is to attenuate sarcopenia by improving atutophagic defect using nutrient- and pharmaceutical-based treatments.


This book discusses recent advances and various topics in plasticity of skeletal muscle from the perspectives of morphology, biological function, and clinical applications. Skeletal muscle is a highly plastic organ to adapt to environmental various demands, appears to endocrine various myokines, which flow into blood to protect the recognizing function of brain and inhibit the appearance of several cancer tumorigenesis.The book deals with current stem-cell based, pharmacological, and nutritional therapies for muscle wasting (sarcopenia, cachexia, and muscular dystrophy). It also explains the roles of biological mediators such as PGC-1, transient receptor potential cation channels (TRPC), and AMPK in modulating muscle function. The functional roles of ubiquitin-proteasome system, autophagy-dependent signaling in muscle homeostasis, ribosome biogenesis, and redox regulation of mechanotransduction to modulate skeletal muscle mass are also covered.It is an essential resource for physicians, researchers, post-docs as well as graduate students in the field of sports science including rehabilitation therapy, exercise physiology, exercise biochemistry, and molecular biology dealing with skeletal muscle.

Professor Kunihiro Sakuma, Ph.D., currently works at Department for Liberal Arts in Tokyo Institute of Technology. He is a Physiologist working in the field of skeletal muscle. He was awarded sports science diploma in 1995 by the University of Tsukuba and started scientific work at the Department of Physiology, Aichi Human Science Center, focusing on the molecular mechanism of congenital muscular dystrophy and normal muscle regeneration. His interest later was turned to the molecular mechanism and the attenuating strategy of sarcopenia (age-related muscle atrophy). Preventing sarcopenia is important for maintaining a high quality of life in the aged population. His opinion is to attenuate sarcopenia by improving atutophagic defect using nutrient- and pharmaceutical-based treatments.

Preface 5
Contents 7
About the Editor 9
1 Pluripotent Stem Cells and Skeletal Muscle Differentiation: Challenges and Immediate Applications 10
1.1 Introduction 11
1.1.1 Human Pluripotent Stem Cells (hPSCs) 11
1.1.1.1 Human Embryonic Stem Cells (hESCs) 11
1.1.1.2 Induced Pluripotent Stem Cells (iPSCs) 13
1.2 General Approaches to Induce In Vitro Differentiation of Pluripotent Stem Cells (PSCs) 16
1.3 Generating Myogenic Cells from Mouse and Human PSCs 22
1.3.1 Exogenous Expression of Muscle-Related Transcription Factors in PSCs: How to Generate Myogenic Precursors and/or Terminally Differentiated Multinucleated Myogenic Cells 22
1.3.2 Generation of Myogenic Precursors and/or Terminally Differentiated Multinucleated Myogenic Cells by Soluble Factors 24
1.4 How to Model Muscle Disease in the Petri Dish 27
1.5 Concluding Remarks 32
References 33
2 Role of the Ubiquitin-Proteasome Pathway in Skeletal Muscle 45
2.1 Introduction 46
2.1.1 Structure of the 26S Proteasome 46
2.1.2 The Ubiquitin-Proteasome System 48
2.1.3 Muscle-Specific Proteasome Dysfunction Mice 49
2.2 Muscle Disease and the Proteasome System 51
2.2.1 Sporadic Inclusion Body Myositis 51
2.2.2 Cachexic State 51
2.2.3 Mutants in the Protein Degradation Systems 52
2.2.4 Proteasomal Abnormality in Other Mutants 53
2.2.5 Nakajo-Nishimura Syndrome and Myositis 53
2.2.6 Motor Neuron Disease 54
2.3 Therapeutic Strategy Using Intervention into the Proteasomal System 55
2.4 Conclusion 57
References 58
3 Stem Cell Therapy in Muscle Degeneration 63
3.1 Introduction: Muscle Damage 64
3.1.1 Necrosis and Chemoattractant Release 64
3.1.2 Inflammatory Response Activation 65
3.1.3 Skeletal Muscle Regeneration: Activation, Proliferation and Fusion of Muscle Precursors 66
3.2 Chronic Inflammation: When the Inflammatory Process Goes Too Far 67
3.2.1 Immune Cell Involvement in Skeletal Muscle Injuries 68
3.2.2 Fibrotic Component in Skeletal Muscle Regeneration 68
3.2.3 Immunomodulatory Drugs 69
3.2.4 Detrimental Effects of Cytokines During Chronic Inflammation 69
3.2.5 Chronic Inflammation in Muscle Degenerative Processes 70
3.3 Stem Cell Therapies in Degenerating Muscles 71
3.3.1 Muscle-Resident Stem Cells 71
3.3.1.1 Satellite Cells (SCs) 71
3.3.1.2 Pericytes/Mesoangioblasts (MABs) 76
3.3.1.3 Muscle-Derived Stem Cells (MDSCs): Skeletal Muscle Aldehyde Dehydrogenase-Positive Cells (ALDH+) and “MuStem Cells” 78
3.3.1.4 PW1-Expressing Interstitial Cells (PICs) 79
3.3.1.5 Muscle Side Population (SP) Cells 79
3.3.1.6 Fibro-/Adipogenic Progenitors (FAPs) 79
3.3.2 Non-resident Stem Cells for Skeletal Muscle Regeneration 80
3.3.2.1 Mesenchymal Stem Cells (MSCs) 80
3.3.2.2 CD133+ Cells 81
3.4 Human Embryonic Stem Cells (ESCs) and Induced Pluripotent Stem Cells (iPSCs): Future Challenges for Stem Cell Therapies 82
3.4.1 Embryonic Stem Cells (ESCs) 82
3.4.2 Induced Pluripotent Stem Cells (iPSCs) 84
3.5 Ex Vivo Cell Therapies 84
3.5.1 Adeno-Associated Virus (AAV) 85
3.5.2 Exon Skipping 85
3.5.3 Reading Through 88
3.5.4 Small Nuclear RNA (snRNA) Sequences 89
3.5.5 Engineered Nucleases 89
3.6 Conclusion 90
References 91
4 The Autophagy-Dependent Signaling in Skeletal Muscle 100
Abbreviations 101
4.1 Introduction 101
4.2 Autophagy-Dependent Signaling 102
4.3 Exercise and Autophagy 103
4.4 Unloading and Autophagy-Dependent System 105
4.5 Autophagic Adaptation in Sarcopenic Muscle 106
4.6 A Marked Contribution of Autophagic Signaling to Cachexia 108
4.7 Autophagic Adaptation in Muscular Dystrophy 111
4.8 The Autophagy and Glucose Metabolism 112
4.9 Concluding Remarks 114
References 115
5 Cytokines in Skeletal Muscle Growth and Decay 119
5.1 Cytokines in Skeletal Muscle Myogenesis and Somatic Growth 120
5.2 Skeletal Muscle Repair and Regeneration 121
5.3 Muscle Injury and Immune Cells 123
5.4 Skeletal Muscle as an Important Source of IL-6 127
5.5 Cytokines Negatively Targeting Skeletal Muscle 130
5.6 Myogenic Myokines 131
5.7 Adipokines in Skeletal Muscle Growth 132
5.8 Conclusions and Perspectives 133
References 134
6 The Role of Ribosome Biogenesis in Skeletal Muscle Hypertrophy 146
6.1 Background 146
6.2 Translation Capacity and Efficiency 147
6.2.1 Translation Capacity in Skeletal Muscle: There and Back Again 148
6.3 Overview of Ribosome Biogenesis 148
6.3.1 rDNA Transcription 149
6.3.2 Upstream Pathways 151
6.4 Ribosome Biogenesis in Skeletal Muscle Hypertrophy and Atrophy 153
6.4.1 Hypertrophy 153
6.4.2 Atrophy 153
6.5 Conclusion and Future Directions 154
References 155
7 Comprehensive Approach to Sarcopenia and Cachexia Treatment 159
7.1 Introduction 160
7.2 Sarcopenia 161
7.2.1 Definition and Epidemiology 161
7.2.2 Diagnostic Criteria 161
7.2.2.1 Muscle Mass 162
7.2.2.2 Muscle Strength 162
7.2.2.3 Physical Performance 163
7.2.3 Causes 163
7.2.3.1 Age-Related Sarcopenia 164
7.2.3.2 Activity-Related Sarcopenia 164
7.2.3.3 Nutrition-Related Sarcopenia 164
7.2.3.4 Disease-Related Sarcopenia 165
7.2.3.5 Complications of All Causes of Sarcopenia 165
7.2.4 Treatment for Sarcopenia 166
7.2.4.1 Age-Related Sarcopenia 166
7.2.4.2 Activity-Related Sarcopenia 167
7.2.4.3 Nutrition-Related Sarcopenia 168
7.2.4.4 Disease-Related Sarcopenia 168
7.3 Cachexia 169
7.3.1 Definition and Epidemiology 169
7.3.2 Diagnostic Criteria 170
7.3.3 Causative Diseases 171
7.3.4 Treatment 172
7.3.4.1 Exercise 172
7.3.4.2 Nutrition Therapy 173
7.3.4.3 Pharmacologic Therapy 173
7.3.4.4 Psychosocial Interventions 174
7.4 Comprehensive Approach 175
7.5 Conclusions 175
References 176
8 The Role and Regulation of PGC-1? and PGC-1? in Skeletal Muscle Adaptation 183
8.1 Introduction 183
8.2 The PGC-1 Family of Transcriptional Coactivators 184
8.3 microRNA Regulation of PGC-1? 185
8.4 Roles of the PGC-1 Family Members in Skeletal Muscle 187
8.5 Mitochondrial Biogenesis 187
8.6 Muscle Fibre Type 188
8.7 Substrate Metabolism 188
8.8 Angiogenesis 189
8.9 Neuromuscular Junction Formation 189
8.10 Inflammation 190
8.11 Expression of the PGC-1 Family Members in Models of Skeletal Muscle Use, Disuse and Disease 190
8.12 Conclusion 192
References 193
9 Characteristics of Skeletal Muscle as a Secretory Organ 199
9.1 Introduction 199
9.2 Muscle-Secreted Proteins as Metabolic Regulators 200
9.3 Muscle-Secreted Proteins and Myogenesis/Osteogenesis 202
9.4 Muscle-Secreted Proteins and Anti-inflammation/Anti-tumorigenesis 204
9.5 Perspective 206
References 208
10 Biological Role of TRPC1 in Myogenesis, Regeneration,and Disease 215
10.1 Introduction 215
10.2 Involvement of TRPC1 in Skeletal Myogenesis 216
10.2.1 Activation of Satellite Cells 216
10.2.2 Migration of Satellite Cells 218
10.2.3 Differentiation of Satellite Cells 219
10.2.4 Regulation of Quiescent Satellite Cells 221
10.3 Involvement of TRPC1 in Muscle Regeneration 222
10.3.1 Muscle Regeneration Following Reduced Mechanical Load 222
10.3.2 Muscle Regeneration Following Injury 224
10.4 Involvement of TRPC1 in Muscular Dystrophy 226
10.5 Concluding Remarks 228
References 228
11 ROS and nNOS in the Regulation of Disuse-Induced Skeletal Muscle Atrophy 235
11.1 Introduction 236
11.2 Models of Disuse 237
11.3 Mechanisms of Disuse-Induced Skeletal Muscle Atrophy 237
11.3.1 Decreased Protein Synthesis and Elevated Protein Degradation 237
11.3.2 Disuse Atrophy Signaling Cascades 238
11.3.3 Novel Disuse-Induced E3 Ubiquitin Ligases 241
11.4 Reactive Oxygen Species (ROS) Production in Skeletal Muscle During Disuse-Induced Atrophy 241
11.4.1 Oxidative Stress and Disuse-Induced Skeletal Muscle Atrophy 241
11.4.2 ROS Production in Skeletal Muscles During Prolonged Periods of Disuse 242
11.4.3 Mechanistic Links Between Oxidative Stress and Disuse-Induced Atrophy 243
11.5 Potential Role of Neuronal Nitric Oxide Synthase-mu During Disuse Atrophy 245
11.6 Conclusions 247
References 248
12 Participation of AMPK in the Control of Skeletal Muscle Mass 255
12.1 Introduction 255
12.2 AMPK: Subunit Structure and Activation Mechanism 257
12.3 AMPK and Skeletal Muscle Hypertrophy 258
12.4 AMPK and Skeletal Muscle Atrophy 259
12.5 Molecular Mechanisms of AMPK-Mediated Regulation of Muscle Mass 260
12.5.1 Protein Synthesis Pathway 260
12.5.2 Ubiquitin–Proteasome System 263
12.5.3 Autophagy 263
12.5.4 Forkhead Box O (FoxOs) 265
12.5.5 Nuclear Factor B (NF-B) 265
12.5.6 Heat Shock Proteins (HSPs) 266
12.5.7 Myostatin 267
12.6 AMPK and Myogenesis 267
12.7 Summary and Perspectives 269
References 270
13 Therapeutic Potential of Skeletal Muscle Plasticity and Slow Muscle Programming for Muscular Dystrophy and Related Muscle Conditions 280
13.1 Introduction 281
13.2 Duchenne Muscular Dystrophy 281
13.3 Skeletal Muscle Diversity and Adaptability 282
13.4 Promoting a Slower, More Oxidative Muscle Phenotype – A Therapeutic Target for DMD 283
13.5 Exercise, Low-Frequency Stimulation and DMD 284
13.6 Pharmacologic Activation to Promote Slow Muscle Programming 286
13.7 Slow Muscle Programming and Protecting Against Muscle Damage 286
13.8 Muscle Plasticity in the Other Direction – Are Slow-to-Fast Muscle Fibre Modifications Contraindicated in Muscular Dystrophy? 288
13.9 Inhibiting Myostatin Signalling 289
13.10 Conclusion 290
References 290

Erscheint lt. Verlag 1.3.2017
Zusatzinfo IX, 292 p. 21 illus., 14 illus. in color.
Verlagsort Singapore
Sprache englisch
Themenwelt Medizin / Pharmazie Medizinische Fachgebiete Orthopädie
Medizin / Pharmazie Medizinische Fachgebiete Sportmedizin
Medizin / Pharmazie Physiotherapie / Ergotherapie Orthopädie
Medizin / Pharmazie Physiotherapie / Ergotherapie Rehabilitation
Medizin / Pharmazie Studium
Technik Bauwesen
Schlagworte Muscle decay • muscle degeneration • Muscle hypertrophy • Muscle protein turnover • Muscular adaptation • Muscular atrophy • Muscular disease • Muscular disorders • Sacropenia
ISBN-10 981-10-3292-0 / 9811032920
ISBN-13 978-981-10-3292-9 / 9789811032929
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