Translational Endocrinology of Bone

Translational Endocrinology of Bone

Reproduction, Metabolism, and the Central Nervous System

1st Edition - October 11, 2012

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  • Editor: Gerard Karsenty
  • eBook ISBN: 9780124158597
  • Hardcover ISBN: 9780124157842

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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.

Key Features

  • 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

Table of Contents

  • Contributors


    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


    Chapter 2. Basic Principles of Bone Cell Biology


    The Osteoblast Lineage


    Bone Remodeling

    Coupling of Bone Formation to Resorption in the BMU

    Bone as an Endocrine Organ



    Chapter 3. The Central Control of Bone Mass



    Sympathetic Nervous System (SNS)


    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


    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



    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




    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


    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


    Chapter 8. Skeletal Actions of Insulin


    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



    Chapter 9. Transcriptional Regulation of the Endocrine Function of Bone


    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



    Chapter 10. Regulation of Bone Resorption by PPARγ


    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




    Chapter 11. From Gonads to Bone, and Back


    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



    Chapter 12. Regulation of Phosphate Metabolism by FGF23


    Phosphate Metabolism

    FGF Biology

    FGF23 and Phosphate Metabolism

    FGF23: Emerging Roles in Disease Processes




    Chapter 13. Clinical Aspects of Fibroblast Growth Factor 23


    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


    Chapter 14. Bone Marrow Fat and Bone Mass


    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


    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



    Chapter 16. Clinical Implications of Serotonin Regulation of Bone Mass


    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


    Considerations for Determination of Causality in Epidemiologic Studies

    Limitations of Current Studies on SSRIS’ Effect on Bone

    Implications for Screening and Population Health



    Chapter 17. Significance of Organ Crosstalk in Insulin Resistance and Type 2 Diabetes


    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




    Color Plates


Product details

  • No. of pages: 236
  • Language: English
  • Copyright: © Academic Press 2012
  • Published: October 11, 2012
  • Imprint: Academic Press
  • eBook ISBN: 9780124158597
  • Hardcover ISBN: 9780124157842

About the Editor

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, USA

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