Front Cover 1
Cellular and Molecular Biology of Bone 4
Copyright Page 5
Table of Contents 6
Contributors 18
Preface 22
CHAPTER 1. OSTEOBLASTIC CELL LINEAGE 24
I. Introduction 25
II. Cells of the Osteoblast Lineage 25
III. Origin and Lineage of the Osteoblast 33
IV. Osteoblast Heterogeneity: Subpopulations, Stages of Differentiation, or Aberrant Expression in Vitro? 39
V. Indirect Identification of the Osteoprogenitor Cell 42
VI. Monoclonal Antibodies for Identification of Cells 
48 
VII. Concluding Remarks 51
References 52
CHAPTER 2. MOLECULAR MECHANISMS MEDIATING DEVELOPMENTAL AND HORMONE-REGULATED EXPRESSION OF GENES IN OSTEOBLASTS: 
70 
I. Introduction 71
II. The Osteoblast Developmental Sequence: A 
72 
III. Hormone Modifications on Development of the Osteoblast Phenotype 82
IV. Molecular Mechanisms Operative in Developmental Expression of a Cell Growth and Bone-Specific Gene during Osteoblast Differentiation 87
V. Consequence of the Abrogation of Growth Controlon Deregulation of Differentiation Genes in Tumor Growth Cells 103
References 108
CHAPTER 3. CELLULAR AND MOLECULAR BIOLOGY OF TRANSFORMING GROWTH FACTOR 
120 
I. Introduction 121
II. Chemistry of Transforming Growth Factor 
121 
III. Multiple Actions of Transforming Growth Factor 
123 
IV. Transforming Growth Factor 
126 
V. Transcriptional Control of Expression of Transforming Growth Factor 
131 
VI. Characterization of the Promoters for Transforming Growth Factors ß1, ß2, and 
135 
VII. Post-transcriptional Regulation of Transforming Growth Factor 
143 
VIII. Conclusion 144
References 145
CHAPTER 4. BONE MORPHOGENETIC PROTEINS AND THEIR GENE EXPRESSION 154
I. Introduction 155
II. Bone Morphogenetic Protein Family 155
III. In Vivo Activities 164
IV. Mechanisms of Action 171
References 180
CHAPTER 5. OUR UNDERSTANDING OF INHERITED SKELETAL FRAGILITY AND WHAT THIS HAS TAUGHT US ABOUT BONE STRUCTURE AND FUNCTION 192
I. Introduction 193
II. Mapping the Osteogenesis Imperfecta Locus 193
III. Clinical Classification 194
IV. Evidence of Genetic and Biochemical Heterogeneity 195
V. Characterization of the First Molecular Defect in a Collagen Gene 196
VI. Mapping Single Amino Acid Substitutions: The Predominant Structural Mutation Associated with Osteogenesis Imperfecta Types II-IV 198
VII. Inheritance 202
VIII. Summary 209
References 209
CHAPTER 6. MOLECULAR AND CELLULAR BIOLOGY OF THE MAJOR NONCOLLAGENOUS PROTEINS IN BONE 214
I. Introduction 215
II. Osteonectin/SPARC/BM-40 216
III. Osteopontin and Bone Sialoprotein 228
IV. Biglycan and Decorin 237
V. Conclusion 244
References 245
CHAPTER 7. THE OSTEOCALCIN GENE AS A MOLECULAR MODEL FOR TISSUE-SPECIFIC EXPRESSION AND 1,25-DIHYDROXYVITAMIN 
258 
I. Introduction 259
II. Osteocalcin Gene Transcription Unit 259
III. Functional Activity of the Osteocalcin Promoter 260
IV Steroid Receptor Superfamily 266
V Role of the Vitamin D Receptor in Osteocalcin Gene Activation 268
VI. Properties of Nuclear Accessory Factor and Other Steroid Receptor Accessory Factors 272
VII. Summary 274
References 275
CHAPTER 8. MOLECULAR MECHANISMS OF ESTROGEN AND THYROID HORMONE ACTION 280
I. Overview of Estrogen and Thyroid Hormone Action 281
II. Characterization of Estrogen- and Thyroid Hormone-Responsive Genes 283
III. Identification and Characterization of Hormone Response Elements 284
IV. Estrogen and Thyroid Hormone Receptor Genes 290
V. DNA-Binding Properties of the Estrogen Receptor 294
VI. DNA-Binding Properties of the Thyroid Hormone Receptor 296
VII. Mechanisms Responsible for Transcriptional Activation by Estrogen and Thyroid Hormone Receptors 298
VIII. Implications for the Study of the Mechanisms of Action of Estrogen and Thyroid Hormones on Bone Development and Homeostasis 300
References 301
CHAPTER 9. RECENT ADVANCES IN THE BIOLOGY OF RETINOIDS 310
I. Introduction 311
II. Retinoid Receptors 314
III. New Retinoids 319
IV. Retinoids in Development 322
V. Conclusion 336
References 336
CHAPTER 10. PARATHYROID HORMONE BIOSYNTHESIS AND ACTION: Molecular Analysis of the Parathyroid Hormone Gene and Parathyroid Hormone/Parathyroid Hormone-Related Peptide Receptor 344
I. Introduction 345
II. Parathyroid Hormone Gene Structure 345
III. Regulation of Parathyroid Hormone Gene Expression 346
IV. Parathyroid Hormone /Parathyroid Hormone-Related Peptide Receptor 351
References 359
CHAPTER 11. MOLECULAR MECHANISMS OF CALCITONIN GENE TRANSCRIPTION AND POST-TRANSCRIPTIONAL RNA PROCESSING 366
I. Introduction 367
II. The Cellular Distribution of Calcitonin and Calcitonin Gene-Related Peptide 367
III. Transcriptional Regulation of the Calcitonin Gene 369
IV. Post-transcriptional Processing of the Calcitonin Gene Primary Transcript 383
References 393
CHAPTER 12. CYTOKINES IN BONE: Local Translators in Cell-to-Cell Communications 398
I. Introduction 399
II. Osteotropic Cytokines and Growth Factors in Bone 399
III. Cellular Components in Bone Microenvironment 400
IV. Mediation of Cell-to-Cell Communication by Osteotropic Cytokines 402
V. Actions of Cytokines and Growth Factors on Bone 405
VI. Conclusion 423
References 424
CHAPTER 13. SIGNAL TRANSDUCTION IN OSTEOBLASTS AND OSTEOCLASTS 436
I. Introduction 437
II. Substances with Effects in Bone Cells 438
III. Mechanisms of Signal Generation 441
IV. Specific Examples of Signal Transduction in Osteoblasts: Parathyroid Hormone/Parathyroid Hormone-Related Peptides 451
V. Specific Examples of Signal Transduction in Osteoclasts 455
References 461
CHAPTER 14. CELLULAR AND MOLECULAR BIOLOGY OF THE OSTEOCLAST 468
I. Introduction 469
II. Motility, Attachment, and Establishment of the Bone Resorbing Compartment 474
III. Proteins Destined for Export: Biosynthetic and Secretory Functions of the Osteoclast 482
IV. Cytosolic and Membrane Proteins: Membrane Composition and Ion Transport 489
V Regulation of the Mature Osteoclast 501
VI. Origin and Differentiation of the Osteoclast 503
VII. A New Challenge: The Protooncogene c-src Is Required for Normal Osteoclast Function 504
VIII. Summary and Conclusion 507
References 507
CHAPTER 15. c-fos ONCOGENE EXPRESSION IN CARTILAGE AND BONE TISSUES OF TRANSGENIC AND CHIMERIC MICE 520
I. Introduction 521
II. The fos Oncogene 526
III. Overexpression of c-fos Leads to Skeletal Defects in Transgenic and Chimeric Mice 532
IV. Specificity of c-fos Action 546
V. Conclusions and Perspectives 551
References 554
CHAPTER 16. MOLECULAR BIOLOGY OF CARTILAGE MATRIX 562
I. Introduction 563
II. Collagen Type II 564
III. Aggrecan 568
IV. Link Protein 573
V. Summary 574
References 575
Index 580