Mechanosensing Biology (eBook)

Masaki Noda (Herausgeber)

eBook Download: PDF
2010 | 2011
XIII, 219 Seiten
Springer Japan (Verlag)
978-4-431-89757-6 (ISBN)

Lese- und Medienproben

Mechanosensing Biology -
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Mechanical stress is vital to the functioning of the body, especially for tissues such as bone, muscle, heart, and vessels. It is well known that astronauts and bedridden patients suffer muscle and bone loss from lack of use. Even the heart, in pumping blood, causes mechanical stress to itself and to vascular tissue. With the loss of mechanical stress, homeostasis becomes impaired and leads to pathological conditions such as osteopenia, muscle atrophy, and vascular tissue dysfunction. In elderly populations, such mechanical pathophysiology, as well as the mechanical activities of locomotor and cardiovascular systems, is important because skeletal and heart functions decline and cause diseases in other organs. In this monograph, mechanical stress is discussed by experts in the field with respect to molecular, cellular, and tissue aspects in relation to medicine. Covering topics such as gravity and tissues and disuse osteoporosis, the book provides the most up-to-date information on cutting-edge advancements in the field of mechanobiology and is a timely contribution to research into locomotor and circulatory diseases that are major problems in contemporary society.


Mechanical stress is vital to the functioning of the body, especially for tissues such as bone, muscle, heart, and vessels. It is well known that astronauts and bedridden patients suffer muscle and bone loss from lack of use. Even the heart, in pumping blood, causes mechanical stress to itself and to vascular tissue. With the loss of mechanical stress, homeostasis becomes impaired and leads to pathological conditions such as osteopenia, muscle atrophy, and vascular tissue dysfunction. In elderly populations, such mechanical pathophysiology, as well as the mechanical activities of locomotor and cardiovascular systems, is important because skeletal and heart functions decline and cause diseases in other organs. In this monograph, mechanical stress is discussed by experts in the field with respect to molecular, cellular, and tissue aspects in relation to medicine. Covering topics such as gravity and tissues and disuse osteoporosis, the book provides the most up-to-date information on cutting-edge advancements in the field of mechanobiology and is a timely contribution to research into locomotor and circulatory diseases that are major problems in contemporary society.

Noda_FM_O.pdf 1
Noda_Ch01_O.pdf 15
Chapter 1: Nanotechnology in Mechanobiology: Mechanical Manipulation of Cells and Organelle While Monitoring Intracellular S 16
1.1 Introduction 16
1.2 A Variety of Methods for Applying Forces to Cells and Analyses of Mechanosensing and Signaling 17
1.2.1 Stretching Cells Cultured on Elastic Sheets 17
1.2.2 Localized Force Application by Dragging a Pipette While Recording Intracellular Signaling 18
1.2.3 Mechanical Force Application to the Cell Surface by Optically Dragging a Bead for Analyzing the Contact Formation 20
1.2.4 Force Application Via a Bead Attached on the Surface of a Cell for the Analyses with High Spatial–Temporal Resolution 21
1.2.5 Mechanical Stretching of Actin Stress Fibers by Displacing a FN-Bead to Activate MS Channels in HUVECs 23
1.2.6 Direct Mechanical Stretching of Actin Stress Fibers by Dragging Beads Optically to Activate MS Channels 26
1.2.7 [Ca2+]i Microdomains in the Vicinity of the FCs Apparently Correspond to the MS Ca2+ Permeable Channels 27
1.3 Roles of Mechanosensing in Cell Migration 29
1.4 Future Perspectives 30
References 30
Noda_Ch02_O.pdf 33
Chapter 2: Molecular Mechanisms Underlying Mechanosensing in Vascular Biology 33
2.1 Introduction 33
2.2 EC Responses to Shear Stress 34
2.3 Shear Stress Mechanotransduction 35
2.3.1 Shear Stress Signaling Pathways 35
2.3.2 Shear Stress Sensors 35
2.3.2.1 Ion Channels 36
P2X4 Channel-Mediated Ca2+ Signaling of Shear Stress 37
Roles of Shear Stress Ca2+ Signaling in Control of Circulatory System 39
2.3.2.2 Tyrosine Kinase Receptors 39
2.3.2.3 G Proteins 40
2.3.2.4 Caveolae 40
2.3.2.5 Adhesion Proteins 41
2.3.2.6 Cytoskeleton 42
2.3.2.7 Glycocalyx 42
2.3.2.8 Primary Cilia 43
2.4 Conclusion 43
References 44
Noda_Ch03_O.pdf 50
Chapter 3: Mechanobiology During Vertebrate Organ Development 50
3.1 Regulation of Neural Crest Cell Migration 50
3.2 Integration of Mechanical Information by Neuronal Cells In Vitro 51
3.3 Differentiation of Pronephros 54
3.4 Effect of Gravity and Shear Stress on Dome Structure Formation in a Tubulogenesis Model 55
References 56
Noda_Ch04_O.pdf 59
Chapter 4: Mechanobiology in Skeletal Muscle: Conversion of Mechanical Information into Molecular Signal 60
4.1 Introduction 60
4.2 Mechanosensor in Skeletal Muscle 61
4.2.1 Experimental Models for Mechanotransduction 61
4.2.2 Mechanosensors in Skeletal Muscle 62
4.2.3 Stretch-Activated Channels 62
4.2.4 Neuronal Nitric Oxide Synthase and Mechanotransduction 63
4.2.5 nNOS and Unloading 64
4.2.6 Phospholipase D and Phosphatidic Acid 65
4.2.7 Integrins/FAK Signaling and Mechanotransduction 65
4.2.8 Sarcomere and Mechanotransduction 66
4.2.9 Growth Factors and Overload 66
4.3 Signaling Pathways in Mechanotransduction 66
4.3.1 mTOR Is a Key Signaling Molecule for Mechanical Overload-Induced Muscle Hypertrophy 67
4.3.2 Unload (Inactivity or Disuse) and the Catabolic Signaling Pathway 67
4.3.2.1 Downstream Targets of NF-kB and FoxO Transcription Factors 68
4.4 Conclusion 68
References 68
Noda_Ch05_O.pdf 72
Chapter 5: Mechanobiology in Space 72
5.1 Introduction 72
5.2 Unloading and Protein Degradation 73
5.3 Muscle Specific Ubiquitin Ligases 74
5.4 Deactivation of IGF-1/PI3K/Akt Pathway 76
5.5 Myostatin 76
5.6 Summary and Perspective 77
References 77
Noda_Ch06_O.pdf 80
Chapter 6: Mechanical Stress and Bone 80
6.1 Introduction 80
6.2 Nervous System Is Involved in Unloading-Induced Bone Loss 81
6.3 Central Control of Bone Mass Under Unloading Condition 83
6.4 Calcium Channel Involvement in Unloading-Induced Bone Loss 84
6.5 Tooth Movement Model and Extracellular Matrix Protein Action in Mechanical Stimulation 85
6.6 Transcription Factor Modulates Unloading-Induced Bone Loss 86
6.7 Unloading-Induced Bone Loss Requires Nucleocytoplasmic Shuttling Protein 87
6.8 Interaction of PTH Signaling and Unloading 89
6.9 Role of Noncollagenous Matrix Protein, OPN, in Bone in Unloading-Induced Bone Loss 91
6.10 Role of Noncollagenous Matrix Protein, OPN in Mechanical Force Dependent Bone Formation 91
6.11 Intracellular Mechanism of Sensing Mechanical Stress 92
6.12 Conclusion 93
References 93
Noda_Ch07_O.pdf 96
Chapter 7: TRP Channels and Mechanical Signals 96
7.1 Transient Receptor Potential Channels 96
7.2 TRPC Channels: Activation by Direct Stretch Via a Lipid-Dependent Mechanism 98
7.3 TRPM Channel: Is It Mechanosensitive? 100
7.4 TRPA1: Activation by Interaction of Cell Cytoskeleton? 101
7.5 TRPV: Activation by Mechanical Stress Through Lipid Metabolites 101
7.6 TRPP2: Making a Flow-Sensing Complex with TRPV4 105
7.7 Hypothesis: Mechanosensitive Channel Complex 106
References 107
Noda_Ch08_O.pdf 111
Chapter 8: Osteoblast Biology and Mechanosensing 112
8.1 Mechanical Forces and Skeletal Integrity 112
8.2 Effects of Mechanical Forces on Osteoblastogenesis 113
8.2.1 Osteoblast Biology 113
8.2.2 Osteoblast Responses to Mechanical Forces 113
8.2.3 Effects of Mechanical Forces on Osteoblastogenesis In Vivo 114
8.3 Mechanosensing Mechanisms in Osteoblasts 117
8.3.1 Mechanical Stimuli 117
8.3.2 Mechanoreceptors 117
8.4 Role of Wnt Signaling in Mechanotransduction in Osteoblasts 120
8.5 Mechanoresponsive Genes in Osteoblasts 120
8.5.1 Transcription Factors 120
8.5.2 Soluble Mediators 121
8.5.3 Growth Factors 123
8.5.4 Matrix Proteins 124
8.6 Conclusions 124
References 125
Noda_Ch09_O.pdf 134
Chapter 9: Osteocytes in Mechanosensing: Insights from Mouse Models and Human Patients 134
9.1 Introduction 134
9.2 Osteocytes in Aging and Disease 134
9.3 Osteocytes in Genetically Modified Mice 136
9.4 Insights from a Mouse Model Lacking Osteocytes 137
9.5 Osteocyte-Derived Factors that Regulate Bone Metabolism 138
9.6 Conclusion 142
References 142
Noda_Ch10_O.pdf 147
Chapter 10: Osteocyte Mechanosensation and Transduction 147
10.1 Introduction 147
10.2 The Osteocyte as a Mechanosensory Cell 148
10.3 In Vitro Cell Culture Models 149
10.4 Cell Body, Cell Process, Cilia 151
10.5 Signaling Pathways Used by Osteocytes in Response to Loading 152
10.6 Role of Integrins in Osteocyte Mechanotransduction 154
10.7 Influence of the Osteocyte Perilacunar Matrix on Mechanosensation 156
10.8 Looking to the Future 157
References 158
Noda_Ch11_O.pdf 162
Chapter 11: Mechanosensing and Signaling Crosstalks 162
11.1 Introduction 163
11.2 Mechanosensors and Signaling Systems 163
11.3 Fos Family Gene Expression in Response to Mechanical Stress 164
11.4 Enhanced IL-11 Expression by Mechanical Stress 166
11.5 Mechanical Stress Upregulates IL-11 Via DFosB/JunD Binding to the AP-1 Site 166
11.6 Smad Signaling in Response to Mechanical Stress 167
11.7 AP-1 and Smad Signaling Pathways Merge on IL-11 Gene Promoter 168
11.8 Stimulation of Canonical Wnt Signaling Downstream IL-11 168
References 169
Noda_Ch12_O.pdf 172
Chapter 12: Osteoblast Development in Bone Loss Due to Skeletal Unloading 172
12.1 Introduction 172
12.2 Materials and Methods 173
12.2.1 Experimental Design 173
12.2.2 Histomorphometry 173
12.2.3 Flow Cytometry 173
12.2.4 Cell Culture 174
12.2.5 ALP Production of Cultured Cells 174
12.2.6 Quantitative Real-Time Reverse-Transcriptase-Polymerase Chain Reactions 174
12.2.7 Statistical Analysis 175
12.3 Results 175
12.3.1 Bone Volume After Unloading and Reloading 175
12.3.2 Bone Volume and Formation in Disrupted p53 Gene 175
12.3.3 PECAM-1 Expression After Unloading 177
12.3.4 Bone Marrow Cell Development 177
12.4 Discussion 178
References 182
Noda_Ch13_O.pdf 184
Chapter 13: Mechanosensing in Bone and the Role of Glutamate Signalling 185
13.1 Introduction 185
13.2 Modes of Loading Affecting the Skeleton 186
13.3 Components of Osteogenic Strains: Strain Magnitude 187
13.4 Strain Rate and Frequency 188
13.5 Strain Direction 189
13.6 Strain Regimen Duration, Repetition and Interruption 190
13.7 Site Specificity of Habitual Bone Strains 190
13.8 Inferences from the Known Effects of Altered Loading 191
13.9 The Role of Glutamate Signalling in the Skeleton’s “Strain Memory” 192
13.10 Conclusions 193
References 193
Noda_Ch14_O.pdf 196
Chapter 14: Osteoclast Biology and Mechanosensing 196
14.1 Introduction 196
14.2 Podosomes: Recently Proven Mechanosensors 199
14.3 Importance of Mechanical Signals During Osteoclast Differentiation 200
14.3.1 Osteoclast Differentiation: The Bone Touch 200
14.3.2 The Need for an Appropriate Experimental System 201
14.3.3 Osteoclast Differentiation Requires a Stiff Substrate 201
14.3.4 Strain Inhibits Osteoclast Differentiation 203
14.3.5 Microgravity Stimulates Osteoclast Differentiation 204
14.4 Importance of Mechanical Signals for Bone Resorption by Osteoclasts 205
14.4.1 Mature Osteoclasts Sense and Respond to Matrix Stiffness 205
14.4.2 Bone Resorption: The Influence of Mechanical Stimulation 206
14.4.3 Can Osteoclasts Recognize and Adapt to Topographical Features? 207
14.5 Molecular Pathways Involved in Osteoclast Response to Mechanical Stimuli 209
14.5.1 Transduction of Mechanical Signal Through Integrin a.vb.3, p130Cas and Src Family Tyrosine Kinases in Osteoclasts? 209
14.5.2 Effectors of Mechanical Signals in Osteoclasts: Myosin IIA and Rho Family GTPases 210
14.6 Conclusion 211
References 212
Noda_Index_O.pdf 217
b978-0-387-78701_4 217

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