Bone and Development (eBook)

Preface 6
Contents 11
Contributors 13
Abbreviations 18
Genetic and Epigenetic Aspects of Bone Development 27
1.1 Introduction 27
1.2 Overview of Human Genetic Disorders of Bone Development 27
1.3 Bone Development 28
1.4 Gene Expression in Osteoblast Development 29
1.5 Gene Expression in Osteoclast Development 31
1.6 Steroid Hormone Receptors in Skeletal Development 33
1.7 Primary Genetic Defects Affecting Bone Development 34
1.8 Epigenetic Regulation in Development 39
1.9 Summary and Conclusions 42
References 43
Tissue Interactions in Long Bone Development 50
2.1 Introduction 50
2.2 Cell Fate Decisions in Early Bone Development 50
2.3 Intrinsic Re gulation of Chondrogenesis and Osteogenesis 51
2.4 Two-Way Interactions Between Cartilage and Bone 54
2.5 Four-Way Interactions Among Cartilage, Bone, Blood Vessels, and Matrix- Resorbing Cells 56
2.6 Are These Tissue Interactions Maintained During Postnatal Life? 58
2.7 Conclusion/Perspectives 59
References 59
The Epiphyseal Growth Plate 63
3.1 Introduction 63
3.2 Growth Plate Architecture, Disposition, and Fusion 64
3.3 Detailed Anatomy and Cellular Dynamics of the Growth Plate 65
3.4 Regulation of Growth Plate Development and Function 68
3.5 Mechanism of Growth-Plate Mineralization 75
3.6 Chondrocyte Metabolism Within the Growth Plate 76
3.7 Deletion of Chondrocytes from the Epiphyseal Growth Plate 77
3.8 Chondrocyte Survival vs. Death: Induction of Autophagy 80
3.9 Diseases of the Growth Plate 82
3.10 Summary 83
References 84
Hedgehog Signaling in Growth Plate and Bone Development 89
4.1 Introduction 89
4.2 The Hedgehog Signaling Pathway 90
4.3 Hh in Human Genetics/ Patterning 92
4.4 Hh in Skeletal Patterning and Craniofacial Development 93
4.5 Ihh in Endochondral Bone Formation 95
4.6 Hh in Joint Formation 98
4.7 Hh in Skeletal Homeostasis 99
Acknowledgments 100
References 100
Role of microRNA in Skeleton Development 105
5.1 What Are miRNAs? 105
5.2 Introduction to Bone Development and Mesenchymal Stem Cells 106
5.3 Mouse Models of Dicer- Dependent Inactivation of miRNA Activity in the early Limb Mesenchyme and the Growth Plate 107
5.4 Evaluation of miRNA Function in the Signaling Pathway that leads to Bone development 107
5.5 An Integrative Model for miRNA Activity in Limb Development 112
Acknowledgment 113
References 113
FGF/FGFR Signaling in Skeletal Dysplasias 116
6.1 Introduction 116
6.2 FGF Signaling in the Growth Plate 116
6.3 Implication of FGF/FGFR Signaling in Chondrodysplasias 118
6.4 FGF Signaling in Cranial Bone 119
6.5 Implication of FGF/FGFR Signaling in Craniosynostosis 120
6.6 Conclusion and Perspectives 122
Acknowledgments 122
References 123
The Role of Hypoxia-Induced Factors 129
7.1 Hypoxia and the Hif Family of Transcription Factors 129
7.2 Hifs and Chondrocytes 133
7.3 Hif-1s and Osteoblasts 137
7.4 Hifs and Osteoclasts 139
7.5 Summary 139
References 139
BMP Signaling in Skeletogenesis 146
8.1 Introduction 146
8.2 The BMP Signaling pathway 146
8.3 BMP Signaling in Mesenchymal Cell Condensation and Commitment to Chondrogenic Lineage 147
8.4 BMP Signaling in Chondrogenesis 148
8.5 BMP Signaling in Osteogenesis 150
8.6 BMP Signaling in Adipogenesis and Energy Metabolism 152
8.7 Perspectives 153
References 153
Wnt Signaling in Bone Development 158
9.1 Introduction 158
9.2 Effects of LRP5 and LRP6 on Bone Formation and Development 159
9.3 Effects of Dkks on Bone Formation and Development 160
9.4 Effects of Kremens on Bone Formation and Development 162
9.5 Effects of SOST/sclerostin on Bone Formation and Development 162
9.6 Effects of Wnts on Bone Formation and Development 163
9.7 Effects of sFRPs on Bone Formation and Development 165
9.8 Effects of Downstream Wnt Pathway Components on Bone Formation and Development 167
9.9 Summary and Conclusions 168
References 169
Development of the Craniofacial Complex 174
10.1 Introduction 174
10.2 Development of the Craniofacial Skeleton 174
10.3 Development of the Mandible 176
10.4 Temporomandibular Joint 180
10.5 Palate Development 182
10.6 Tooth Development 189
10.7 Future Perspectives 194
Acknowledgment 194
References 195
Dentin and Bone: Similar Collagenous Mineralized Tissues 203
11.1 Odontogenesis 203
11.2 Osteogenesis 206
11.3 Cell Lines and Models of Osteoblast and Odontoblast Cultures 207
11.4 Transcriptional Control of Osteoblast and Odontoblast Differentiation 209
11.5 Composition of Matrix Synthesized by Osteoblasts and Odontoblasts 210
11.6 Genetic Syndromes and Diseases 213
11.7 Common Properties of Bone and Dentin 214
References 215
Evolution of Bone Proteins 221
12.1 Introduction 221
12.2 Gene Duplication 221
12.3 Collagens 222
12.4 BGP and MGP 224
12.5 Secretory Calcium-Binding Phosphoproteins 225
12.6 Small Leucine-Rich Proteoglycans 228
12.7 Directed Evolution of Apatite Binding Peptides 228
12.8 Value and Application of Evolutionary Studies 230
12.9 Conclusion 230
Acknowledgment 230
References 230
Osteogenesis Imperfecta 235
13.1 Introduction 235
13.2 Nosology and Biology 235
13.3 Clinical Approach 238
13.4 Differential Diagnosis 240
13.5 Testing for Osteogenesis Imperfecta 241
13.6 Biochemistry 242
13.7 Imaging 242
13.8 Histomorphometry 242
13.9 Medical Therapy 243
13.10 Management of Severely Affected Infants 246
13.11 Problems in Adulthood 246
13.12 Future Prospects 247
References 247
Fibrodysplasia Ossificans Progressiva: Developmental Implications of a Novel Metamorphogene 252
14.1 Introduction 252
14.2 Clinical Features of Classic FOP 252
14.3 Diagnosis and Misdiagnosis of FOP 253
14.4 Epidemiologic, Genetic, and Environmental Factors in FOP 254
14.5 FOP and the BMP Signaling Pathway 254
14.6 The FOP Gene 254
14.7 Atypical FOP Phenotypes Caused by Novel Mutations in the FOP Gene 255
14.8 Protein Homology Mapping of the FOP Gene 255
14.9 FOP and Morphogenesis 259
14.10 FOP and Metamorphosis 260
14.11 FOP and Oncogenesis 261
14.12 FOP and Degenerative Joint Disease 263
14.13 Prevention and Treatment of Skeletal Metamorphosis in FOP 264
14.14 Conclusions 264
Acknowledgments 265
References 265
Bone-Mineral Homeostasis and Associated Pathologies 269
15.1 Introduction 269
15.2 Physiological Aspects 269
15.3 Pathophysiological Aspects 271
15.4 Pathogenesis of Vitamin D and Calcium Insufficiency- Related Diseases 273
15.5 Conclusion 278
References 279
Interrelationship Between Bone and Other Tissues: Brain– Bone Axis and Bone- Adipo Axis 284
16.1 Introduction 284
16.2 Leptin and Bone 284
16.3 Regulation of Bone Remodeling by Leptin 285
16.4 Leptin and Bone Remodeling in Human Subjects 286
16.5 Leptin, the Sympathetic Nervous System, and Bone Remodeling 286
16.6 SNS and Bone Remodeling: Clinical Implications 287
16.7 Regulation of Bone Remodeling by Neuropeptides Affecting Appetite: Cocaine-and Amphetamine- Regulated Transcript ( Cart) and MC4R 287
16.8 The Melanocortin 4 Receptor 288
16.9 Neuromedin U 288
16.10 Npy 289
16.11 Regulation of Glucose Metabolism by Bone Cells 289
16.12 Osteocalcin as a Potential Therapeutic for Diabetes 291
16.13 Leptin Regulates Glucose Metabolism Through Osteoblasts via the SNS 292
16.14 Clinical Implications of the Skeletal Regulation of Glucose Metabolism 292
16.15 Conclusions 293
References 293
Mechanobiology of Bone Development and Computational Simulations 296
17.1 Form and Function of Bone 296
17.2 Mechanobiological Regulation and Simulations of Bone Growth 299
17.3 Mechanobiological Regulation of Bone Remodeling and Bone Remodeling Simulations 302
17.4 Mechanobiological Regulation and Simulations of Bone Fracture Healing 305
17.5 Summary 308
Acknowledgments 309
References 309
Subject Index 313