Translational Endocrinology of Bone
Reproduction, Metabolism, and the Central Nervous System
- 1st Edition - October 11, 2012
- Editor: Gerard Karsenty
- Language: English
- Hardback ISBN:9 7 8 - 0 - 1 2 - 4 1 5 7 8 4 - 2
- eBook ISBN:9 7 8 - 0 - 1 2 - 4 1 5 8 5 9 - 7
The use of model organisms together with the power of genetics has profoundly affected our understanding of the physiology of one organ, the skeleton, in two distinct but… Read more
The use of model organisms together with the power of genetics has profoundly affected our understanding of the physiology of one organ, the skeleton, in two distinct but complementary ways. This is the first translational reference to focus on these major conceptual advances in bone biology and their development in the clinic. Several advances have already been translated into therapies and others are being tested for diseases as different as osteoporosis, type-2 diabetes, and hypo-fertility. This book is a timely reference for both basic and clinical researchers in bone biology and endocrinology.
- Summarizes the latest research and translational applications of how the varied growth and development of bone affects appetite, metabolism, reproduction, and a wide range of endocrine functions
- Provides a common language for bone biologists, endocrinologists, osteologists, and other researchers, such as neuroscientists, who study appetite, fuel metabolism and diabetes, to discuss the development of translational research and new therapeutic strategies for bone, metabolic, and neuro-endocrine diseases
- Saves researchers and clinicians time in quickly accessing the very latest details on a broad range of bone research and therapeutics, as opposed to searching through thousands of journal articles
Clinical and basic researchers in bone biology and clinician researchers in endocrinology, osteology, rheumatology, and orthopedic surgery
Contributors
Foreword
Chapter 1. Introduction: The Rational of the Work or the Overarching Hypothesis
The Two Faces of Physiology
The Unanticipated Influence of Bone on Whole-Organism Physiology
References
Chapter 2. Basic Principles of Bone Cell Biology
Introduction
The Osteoblast Lineage
Osteoclasts
Bone Remodeling
Coupling of Bone Formation to Resorption in the BMU
Bone as an Endocrine Organ
Acknowledgments
References
Chapter 3. The Central Control of Bone Mass
Introduction
Leptin
Sympathetic Nervous System (SNS)
Serotonin
Neuromedin U
Neuropeptide Y (NPY) and NPY Receptors
Cocaine- and Amphetamine-Regulated Transcripts
Melanocortin and MC4R
The Cannabinoid System
Other Central Hormones and Neuropeptides Regulating Bone Remodeling
References
Chapter 4. Neuropeptide Y and Bone Formation
The Neuropeptide Y System
Neuropeptide Y and Bone Homeostasis
Other NPY Ligands
The NPY Receptors
NPY Interaction with Leptin in the Control of Bone Homeostasis
NPY’S Coordination of Body Weight and Bone Mass
Interactions Between NPY and Sex Hormones in the Control of Bone Homeostasis
Conclusion
References
Chapter 5. Serotonin: The Central Link between Bone Mass and Energy Metabolism
Energy Metabolism and its Regulation
Perturbations in Energy Metabolism and Bone Mass
Discovery of Leptin Regulation of Bone Mass
Gain of Function of Leptin Signaling and Bone Mass
Factors Downstream of Leptin Regulation of Bone Mass
Leptin Acts in the Brain to Regulate Bone Mass
Neurotransmitter Profiling in Leptin-Deficient Mice Brain Points to Serotonin as a Target of Leptin
Serotonin Uses Creb in Arc and Vmh Neurons to Regulate Two Different Functions
Leptin Receptor Deletion on Serotonin Nuclei Results in Increased Appetite
Perspective
Acknowledgment
References
Chapter 6. Gastrointestinal Tract and the Control of Bone Mass
The Relevance of the Gastrointestinal Tract for the Skeleton
Hypochlorhydria, a Major Public Health Problem
Proton Pump Inhibitors and Osteoporosis
How are Proton Pump Inhibitors Affecting the Skeleton?
Gastrectomy and Osteomalacia, an Association not to be Forgotten
Osteopetrorickets, a Rare Disorder Caused by a Combined Acidification Defect of Osteoclasts and Parietal Cells
Animal Models of Impaired Gastric Acidification
Calcium Supplementation in Clinical Practice
Concluding Remarks
References
Chapter 7. Gut-derived Serotonin and Bone Formation
Serotonin: A Tale of Guts and Brain
Regulation of Bone Formation by Gut-Derived Serotonin
Regulation of Serotonin Production in Gut by Lrp5
Regulation of Bone Formation by Serotonin in Humans
Modulation of Tph1 Activity as a Novel Bone Anabolic Therapy
References
Chapter 8. Skeletal Actions of Insulin
Introduction
The Insulin/IGF Family of Ligands and Receptors
Actions of IGF-1 and Insulin in Osteoblasts
Insulin Signaling in the Osteoblasts Regulates Glucose Metabolism
Insulin Signaling Regulates Osteocalcin Production and Bioavailability
From Mouse to Man
Perspectives and Directions for Future Studies
Acknowledgments
References
Chapter 9. Transcriptional Regulation of the Endocrine Function of Bone
Introduction
Foxo1, A Transcriptional Modulator of the Endocrine Function of the Skeleton
Atf4 in Skeletal Regulation of Energy Homeostasis
ΔFosb Reciprocally Affects Bone Mass and Fat Accrual and Favors Insulin Sensitivity
Creb Versus Atf4 in Central Control of Bone Mass: Leptin
Creb in Central Versus Local Control of Bone Formation: Serotonin
Creb in Bone Regulation of Male Reproduction
Perspective
References
Chapter 10. Regulation of Bone Resorption by PPARγ
Introduction
PPARγ Expression Specifies Osteoclast Progenitor
PPARγ Activation Stimulates Osteoclast Differentiation by Inducing C-FOS
PPARγ Activation Stimulates Osteoclast Differentiation by Downregulating β-Catenin
PPARγ Activation Promotes Osteoclastogenesis by Activating PGC1β and ERRα
Other Signaling Pathways that may Intersect with PPARγ During Osteoclastogenesis
TZDS Induce Bone Loss by Activating Bone Resorption and Inhibiting Bone Formation
Systemic PPARγ Activation Enhances Bone Resorption by Both Osteoclast-Autonomous and Non-Autonomous Mechanisms
PPARγ Effects on Bone Resorption are Context Dependent
Conclusion
Acknowledgments
References
Chapter 11. From Gonads to Bone, and Back
Introduction
Sex Steroid Hormones Effects on Bone Physiology
Sex Steroid Hormone Regulation of Bone Growth
Sex Steroid Hormone Regulation of Bone Mass Maintenance
Estrogen and Androgen Mode of Action in Skeleton
Genomic and Non-Genomic Sex Steroid Hormone Signaling in Bone Cells
Osteocalcin, a New Player in the Regulation of Testosterone Production
Osteocalcin Mode of Action in Leydig Cells
Correlative Observation of the Osteocalcin-Dependent Regulation of Testosterone Production in Humans
Disturbances in Osteocalcin or its Receptor Activity are Associated to Prostate Cancer
Conclusion
References
Chapter 12. Regulation of Phosphate Metabolism by FGF23
Introduction
Phosphate Metabolism
FGF Biology
FGF23 and Phosphate Metabolism
FGF23: Emerging Roles in Disease Processes
Summary
Acknowledgments
References
Chapter 13. Clinical Aspects of Fibroblast Growth Factor 23
Introduction
Hypophosphatemic Diseases
Treatment of FGF23-Related Hypophosphatemic Diseases
Tumoral Calcinosis
Chronic Kidney Disease–Mineral and Bone Disorder (CKD–MBD)
FGF23 in Epidemiological Studies
Future Direction
References
Chapter 14. Bone Marrow Fat and Bone Mass
Introduction
Historical Vignette
Molecular and Cellular Aspects of Marrow Adipogenesis
Development of Marrow Fat
The Function of Marrow Fat
Mouse Models to Study Marrow Adipocytes
Marrow Fat in Humans
Future Direction
References
Chapter 15. Osteocalcin, Undercarboxylated Osteocalcin, and Glycemic Control in Human Subjects
Obesity, Diabetes, and Low Serum Osteocalcin: Cross-Sectional Studies in Human Subjects
Osteocalcin and Glycemic Control: Interventional Studies
Interventional Studies Manipulating Vitamin K Levels
What is the Active Form of Osteocalcin in Humans?
Endosteal Surface Area, Remodeling, and Glycemic Control
Osteocalcin and Glycemic Control: Conclusions and Clinical Implications
Acknowledgments
References
Chapter 16. Clinical Implications of Serotonin Regulation of Bone Mass
Introduction
Synthesis and Function of Serotonin in the Nervous System
Studies of Serotonin Influence on Bone in Human Development
Clinical Studies Demonstrating an Effect of Serotonin on Bone in Adults
Bone Density
Fractures
Considerations for Determination of Causality in Epidemiologic Studies
Limitations of Current Studies on SSRIS’ Effect on Bone
Implications for Screening and Population Health
Conclusion
References
Chapter 17. Significance of Organ Crosstalk in Insulin Resistance and Type 2 Diabetes
Introduction
Mechanisms of β-Cell Failure/Loss
Insulin Resistance—Multiorgan Crosstalk of Insulin Target Tissues
Non-Canonical Insulin Target Tissues
Therapy for Type 2 Diabetes Mellitus
Perspective
Acknowledgments
References
Color Plates
Index
- Edition: 1
- Published: October 11, 2012
- Language: English
GK
Gerard Karsenty
Gerard Karsenty received his MD and PhD from the University of Paris, France and completed his post-doctoral training at the University of Texas MD Anderson Cancer Center in 1990. His laboratory has studied every aspect of skeletal biology ranging from cell differentiation to function. His laboratory was the first one to decipher the molecular bases of osteoblast-specific gene expression, work that culminated in the identification of Runx2 as the master gene of osteoblast differentiation. The overarching assumption of Dr. Karsenty’s work is that the appearance of bone during evolution has profoundly changed the physiology of animals because of the energetic cost that bone growth entails. Thus, over the last 10 years, his group has explored the hypothesis that the control of bone mass and energy metabolism must be coordinated and that this coordination is done, in large part, by hormones like leptin and osteocalcin that appear during evolution with bone. His lab has explored every aspect of this hypothesis through genetic and molecular means. Concurrent with this research, the Karsenty lab is exploring whether there are additional connections between bone physiology and the function of other organs such as fertility. This work culminated in the discovery that bone, via osteocalcin, regulates testosterone production.
Affiliations and expertise
Professor and Chair, Department of Genetics and Development, Columbia University Medical School, New York, NY, USARead Translational Endocrinology of Bone on ScienceDirect