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Table of Contents
9780128130742v1_WEB
Front Cover
Marcus and Feldman's Osteoporosis
Copyright Page
Volume 1 Contents
Volume 2 Contents
List of contributors
Foreword
I. Introduction
1 The nature of osteoporosis
1.1 Defining osteoporosis
1.2 Material and structural basis of skeletal fragility
1.2.1 Role of bone microarchitecture
1.3 Role of bone matrix properties
1.3.1 Matrix mineralization
1.3.2 Collagen characteristics
1.3.3 Microdamage
1.4 Summary
References
Further reading
2 The bone organ system: form and function
2.1 Introduction
2.2 Composition and organization of bone
2.2.1 Organic phase
2.2.2 Inorganic phase
2.2.3 Organization of bone
2.3 Cellular components of bone
2.3.1 Bone cells
2.3.2 Mesenchymal lineage cells
2.3.3 The hematopoietic cell lineage
2.4 Bone homeostasis
2.4.1 Osteoblast-osteoclast coupling
2.4.2 Bone remodeling
2.5 Basic bone mechanics
2.5.1 Mechanical behavior of whole bones
2.5.2 Mechanical behavior of bone tissue
2.6 Summary
References
II. Developmental, cellular and molecular biology of bone
3 Development of the skeleton
3.1 Overview
3.2 Patterning the skeleton
3.2.1 Axial skeleton development
3.2.2 Craniofacial bone development
3.2.3 Appendicular/limb development
3.2.3.1 Formation of the early limb
3.2.3.2 Proximal-distal patterning of the limb
3.2.3.3 The anteroposterior patterning of the limb
3.2.3.4 Dorso-ventral patterning of the limb
3.2.3.5 Mesenchymal condensation and limb patterning
3.2.3.6 Joint formation and limb patterning
3.3 Endochondral bone development
3.3.1 Chondrocytes
3.3.2 Osteoblasts
3.3.3 Osteoclasts
3.3.4 Signaling pathways that regulate endochondral bone formation
3.3.5 Bone morphogenetic protein signaling
3.3.6 Wnt signaling.
3.3.7 Fibroblast growth factor, C-type natriuretic peptide, and mitogen-activated protein kinase signaling
3.3.7.1 Fgf signaling in endochondral bone development
3.3.7.2 Mitogen-activated protein kinase signaling in endochondral bone development
3.3.8 Indian hedgehog and parathyroid hormone-related protein signaling
3.3.9 Vascular endothelial growth factor signaling
3.3.10 Delta/Notch signaling
3.4 Intramembranous bone formation
References
4 The skeletal stem cell
4.1 Introduction
4.2 Defining skeletal stem cells
4.2.1 Developmental origin of bone and skeletal stem cells
4.2.2 Isolation and identification of skeletal stem cells
4.2.3 Heterogeneity of skeletal stem cells in adult bones
4.3 Migration of skeletal stem cells
4.4 Kinetics of skeletal cell turnover
4.4.1 Osteoblast kinetics
4.4.2 Osteoblasts are postmitotic
4.4.3 Osteocyte kinetics
4.4.4 Turnover of other osteolineage cell types
4.5 Potential use of skeletal stem cells as therapy
4.6 Interactions with the hematopoietic system
4.6.1 The endosteal hematopoietic niche
4.6.2 Hematopoietic regulation of the endosteal niche
4.6.3 Perivascular skeletal stem cells-the perivascular niche
4.6.4 The vascular niche
4.6.5 The bone marrow environment is hypoxic
4.6.6 Nervous system mediators
4.7 Conclusion
References
5 Osteoclast biology
5.1 Introduction
5.2 Regulation of osteoclast formation
5.2.1 Early research
5.2.2 Intracellular and transmembrane factors
5.2.3 RANKL-RANKL-OPG axis
5.2.4 Other local and systemic factors
5.2.5 Hypoxia
5.3 Osteoclast function
5.3.1 Recruitment
5.3.2 Attachment, polarization, and resorption
5.3.3 Osteoclast activation
5.3.4 Osteoclast survival
5.3.5 Osteoclast metabolism
5.3.6 Osteoclast substrates and resorption environment.
5.4 Conclusion
Financial support
Potential conflicts of interest
References
6 Osteoblast biology: developmental origin and interactive nature of osteoblasts
6.1 Developmental origin of osteoblasts
6.1.1 Control of osteoblast function
6.1.1.1 Signaling pathways that control bone formation
6.1.1.2 Transcriptional mechanisms that regulate osteogenic lineage commitment and osteoblast differentiation
6.1.1.3 Epigenetic regulation of bone formation and osteoblastogenesis
6.1.2 Morphology
6.1.2.1 Osteoblasts
6.1.2.2 Osteocytes
6.1.2.3 Bone lining cells
6.1.3 Extracellular matrix
6.1.3.1 Collagenous proteins
6.1.3.2 Noncollagenous proteins
6.1.3.3 Matrix mineralization
6.2 Interactive nature of osteoblasts
6.2.1 Cell-matrix interaction
6.2.2 Paracrine actions
6.2.2.1 Osteoblast-osteoclast interaction
6.2.2.2 Osteoblasts in the hematopoietic stem cell niche
6.2.2.3 Osteoblasts-endothelial cell cross talk and fracture healing
6.2.2.4 Osteoimmunology
6.2.3 Endocrine actions
6.2.3.1 Phosphate homeostasis (fibroblast growth factor 23)
6.2.3.2 Glucose metabolism (osteocalcin)
6.2.3.3 Appetite (lipocalin 2)
6.2.3.4 Fat metabolism (sclerostin)
References
7 Osteocytes
7.1 Introduction
7.2 Osteocyte ontogeny
7.3 Osteoid-osteocytes
7.4 Osteocyte-selective genes/proteins and their potential functions
7.5 Morphology of osteocytes: lacunocanalicular system and dendrite formation
7.6 Osteocyte cell models
7.7 Mechanisms and response of osteocytes to mechanical forces
7.8 Osteocyte signals for bone formation
7.9 Osteocyte signals for bone resorption
7.10 Osteocyte apoptosis and autophagy
7.11 Osteocyte modification of their microenvironment
7.12 Osteocyte regulation of phosphate metabolism
7.13 Osteocyte communication with muscle.
7.14 Role of gap junctions and hemichannels in osteocyte communication
7.15 Osteocytes in the embryonic and the adult skeleton with aging
7.16 The implications of osteocyte biology for bone disease
7.17 Conclusion
Acknowledgment
References
8 The regulatory role of matrix proteins in mineralization of bone
8.1 Introduction
8.1.1 Bone tissue: composition
8.1.2 Bone mineral
8.2 Collagenous proteins
8.2.1 Structure of the collagen molecule
8.2.2 Bone matrix collagen(s)
8.3 Intermediate cartilage matrix
8.3.1 Large proteoglycans
8.3.1.1 Aggrecan
8.3.1.2 Versican
8.3.2 Small leucine-rich repeat proteoglycans
8.3.3 Class I small leucine-rich repeat proteoglycans associated with mineralization
8.3.3.1 Decorin
8.3.3.2 Biglycan
8.3.3.3 Asporin
8.3.4 Class II small leucine-rich repeat proteoglycans associated with mineralization
8.3.4.1 Fibromodulin
8.3.4.2 Osteomodulin, keratocan, and lumican
8.3.5 Class III small leucine-rich repeat proteoglycans involved in mineralization
8.3.5.1 Epiphycan
8.3.5.2 Chondroadherin
8.4 Bone-enriched matrix proteins
8.4.1 Glycoproteins
8.4.1.1 Alkaline phosphatase
8.4.1.2 Osteonectin
8.4.1.3 RGD-containing glycoproteins
8.4.2 γ-Carboxyglutamic acid-containing proteins
8.4.2.1 Osteocalcin
8.4.2.2 Matrix γ-carboxyglutamic acid protein
8.4.2.3 Periostin
8.5 The mineralization of bone matrix
8.5.1 Nucleation and growth of mineral crystals
8.5.2 Mineral structure and interaction with the organic matrix
8.5.3 Mineral homeostasis regulation by bone cells
Acknowledgments
References
III. Skeletal hormones and regulatory factors
9 Parathyroid hormone and parathyroid hormone-related protein
9.1 Introduction
9.2 Synthesis and secretion of parathyroid hormone
9.3 Metabolism of parathyroid hormone.
9.4 Bone-resorbing action of parathyroid hormone
9.5 Effects of parathyroid hormone on bone formation
9.6 Renal actions of parathyroid hormone
9.7 Parathyroid hormone-related protein as a mediator of humoral hypercalcemia of malignancy
9.8 Physiological roles of parathyroid hormone-related protein
9.8.1 Endochondral bone development
9.8.2 Bone
9.8.3 Mammary gland
9.8.4 Skin and teeth
9.8.5 Other actions of parathyroid hormone-related protein
9.9 Mechanism of action of parathyroid hormone and parathyroid hormone-related protein
Acknowledgment
References
10 Phosphatonins
10.1 Introduction
10.2 Phosphorus homeostasis
10.2.1 Role of the kidney in phosphate homeostasis
10.2.2 Role of the intestine in phosphate homeostasis
10.3 Phosphatonins
10.4 Fibroblast growth factor 23
10.4.1 Hypophosphatemic disorders with defective mineralization
10.4.1.1 Autosomal dominant hypophosphatemic rickets
10.4.1.2 Tumor-induced osteomalacia
10.4.1.3 X-linked hypophosphatemic rickets
10.4.1.3.1 Antifibroblast growth factor 23 antibody therapy
10.4.1.4 Fibrous dysplasia/McCune Albright
10.4.2 Hyperphosphatemic disorders
10.4.2.1 Tumoral calcinosis
10.4.2.2 Chronic kidney disease
10.4.3 Effects of fibroblast growth factor 23 in the kidney and intestine
10.4.4 Fibroblast growth factor 23 and Klotho
10.4.5 Effects of fibroblast growth factor 23 in bone
10.4.6 Fibroblast growth factor 23 in normal phosphate homeostasis
10.5 Secreted frizzled-related protein 4
10.6 Matrix extracellular phosphoglycoprotein
10.7 Fibroblast growth factor 7
10.8 Summary
References
11 Skeletal growth factors
Abbreviations
11.1 Introduction
11.2 Platelet-derived growth factor
11.3 Vascular endothelial growth factor
11.4 Fibroblast growth factor.
11.5 Transforming growth factor beta.
Front Cover
Marcus and Feldman's Osteoporosis
Copyright Page
Volume 1 Contents
Volume 2 Contents
List of contributors
Foreword
I. Introduction
1 The nature of osteoporosis
1.1 Defining osteoporosis
1.2 Material and structural basis of skeletal fragility
1.2.1 Role of bone microarchitecture
1.3 Role of bone matrix properties
1.3.1 Matrix mineralization
1.3.2 Collagen characteristics
1.3.3 Microdamage
1.4 Summary
References
Further reading
2 The bone organ system: form and function
2.1 Introduction
2.2 Composition and organization of bone
2.2.1 Organic phase
2.2.2 Inorganic phase
2.2.3 Organization of bone
2.3 Cellular components of bone
2.3.1 Bone cells
2.3.2 Mesenchymal lineage cells
2.3.3 The hematopoietic cell lineage
2.4 Bone homeostasis
2.4.1 Osteoblast-osteoclast coupling
2.4.2 Bone remodeling
2.5 Basic bone mechanics
2.5.1 Mechanical behavior of whole bones
2.5.2 Mechanical behavior of bone tissue
2.6 Summary
References
II. Developmental, cellular and molecular biology of bone
3 Development of the skeleton
3.1 Overview
3.2 Patterning the skeleton
3.2.1 Axial skeleton development
3.2.2 Craniofacial bone development
3.2.3 Appendicular/limb development
3.2.3.1 Formation of the early limb
3.2.3.2 Proximal-distal patterning of the limb
3.2.3.3 The anteroposterior patterning of the limb
3.2.3.4 Dorso-ventral patterning of the limb
3.2.3.5 Mesenchymal condensation and limb patterning
3.2.3.6 Joint formation and limb patterning
3.3 Endochondral bone development
3.3.1 Chondrocytes
3.3.2 Osteoblasts
3.3.3 Osteoclasts
3.3.4 Signaling pathways that regulate endochondral bone formation
3.3.5 Bone morphogenetic protein signaling
3.3.6 Wnt signaling.
3.3.7 Fibroblast growth factor, C-type natriuretic peptide, and mitogen-activated protein kinase signaling
3.3.7.1 Fgf signaling in endochondral bone development
3.3.7.2 Mitogen-activated protein kinase signaling in endochondral bone development
3.3.8 Indian hedgehog and parathyroid hormone-related protein signaling
3.3.9 Vascular endothelial growth factor signaling
3.3.10 Delta/Notch signaling
3.4 Intramembranous bone formation
References
4 The skeletal stem cell
4.1 Introduction
4.2 Defining skeletal stem cells
4.2.1 Developmental origin of bone and skeletal stem cells
4.2.2 Isolation and identification of skeletal stem cells
4.2.3 Heterogeneity of skeletal stem cells in adult bones
4.3 Migration of skeletal stem cells
4.4 Kinetics of skeletal cell turnover
4.4.1 Osteoblast kinetics
4.4.2 Osteoblasts are postmitotic
4.4.3 Osteocyte kinetics
4.4.4 Turnover of other osteolineage cell types
4.5 Potential use of skeletal stem cells as therapy
4.6 Interactions with the hematopoietic system
4.6.1 The endosteal hematopoietic niche
4.6.2 Hematopoietic regulation of the endosteal niche
4.6.3 Perivascular skeletal stem cells-the perivascular niche
4.6.4 The vascular niche
4.6.5 The bone marrow environment is hypoxic
4.6.6 Nervous system mediators
4.7 Conclusion
References
5 Osteoclast biology
5.1 Introduction
5.2 Regulation of osteoclast formation
5.2.1 Early research
5.2.2 Intracellular and transmembrane factors
5.2.3 RANKL-RANKL-OPG axis
5.2.4 Other local and systemic factors
5.2.5 Hypoxia
5.3 Osteoclast function
5.3.1 Recruitment
5.3.2 Attachment, polarization, and resorption
5.3.3 Osteoclast activation
5.3.4 Osteoclast survival
5.3.5 Osteoclast metabolism
5.3.6 Osteoclast substrates and resorption environment.
5.4 Conclusion
Financial support
Potential conflicts of interest
References
6 Osteoblast biology: developmental origin and interactive nature of osteoblasts
6.1 Developmental origin of osteoblasts
6.1.1 Control of osteoblast function
6.1.1.1 Signaling pathways that control bone formation
6.1.1.2 Transcriptional mechanisms that regulate osteogenic lineage commitment and osteoblast differentiation
6.1.1.3 Epigenetic regulation of bone formation and osteoblastogenesis
6.1.2 Morphology
6.1.2.1 Osteoblasts
6.1.2.2 Osteocytes
6.1.2.3 Bone lining cells
6.1.3 Extracellular matrix
6.1.3.1 Collagenous proteins
6.1.3.2 Noncollagenous proteins
6.1.3.3 Matrix mineralization
6.2 Interactive nature of osteoblasts
6.2.1 Cell-matrix interaction
6.2.2 Paracrine actions
6.2.2.1 Osteoblast-osteoclast interaction
6.2.2.2 Osteoblasts in the hematopoietic stem cell niche
6.2.2.3 Osteoblasts-endothelial cell cross talk and fracture healing
6.2.2.4 Osteoimmunology
6.2.3 Endocrine actions
6.2.3.1 Phosphate homeostasis (fibroblast growth factor 23)
6.2.3.2 Glucose metabolism (osteocalcin)
6.2.3.3 Appetite (lipocalin 2)
6.2.3.4 Fat metabolism (sclerostin)
References
7 Osteocytes
7.1 Introduction
7.2 Osteocyte ontogeny
7.3 Osteoid-osteocytes
7.4 Osteocyte-selective genes/proteins and their potential functions
7.5 Morphology of osteocytes: lacunocanalicular system and dendrite formation
7.6 Osteocyte cell models
7.7 Mechanisms and response of osteocytes to mechanical forces
7.8 Osteocyte signals for bone formation
7.9 Osteocyte signals for bone resorption
7.10 Osteocyte apoptosis and autophagy
7.11 Osteocyte modification of their microenvironment
7.12 Osteocyte regulation of phosphate metabolism
7.13 Osteocyte communication with muscle.
7.14 Role of gap junctions and hemichannels in osteocyte communication
7.15 Osteocytes in the embryonic and the adult skeleton with aging
7.16 The implications of osteocyte biology for bone disease
7.17 Conclusion
Acknowledgment
References
8 The regulatory role of matrix proteins in mineralization of bone
8.1 Introduction
8.1.1 Bone tissue: composition
8.1.2 Bone mineral
8.2 Collagenous proteins
8.2.1 Structure of the collagen molecule
8.2.2 Bone matrix collagen(s)
8.3 Intermediate cartilage matrix
8.3.1 Large proteoglycans
8.3.1.1 Aggrecan
8.3.1.2 Versican
8.3.2 Small leucine-rich repeat proteoglycans
8.3.3 Class I small leucine-rich repeat proteoglycans associated with mineralization
8.3.3.1 Decorin
8.3.3.2 Biglycan
8.3.3.3 Asporin
8.3.4 Class II small leucine-rich repeat proteoglycans associated with mineralization
8.3.4.1 Fibromodulin
8.3.4.2 Osteomodulin, keratocan, and lumican
8.3.5 Class III small leucine-rich repeat proteoglycans involved in mineralization
8.3.5.1 Epiphycan
8.3.5.2 Chondroadherin
8.4 Bone-enriched matrix proteins
8.4.1 Glycoproteins
8.4.1.1 Alkaline phosphatase
8.4.1.2 Osteonectin
8.4.1.3 RGD-containing glycoproteins
8.4.2 γ-Carboxyglutamic acid-containing proteins
8.4.2.1 Osteocalcin
8.4.2.2 Matrix γ-carboxyglutamic acid protein
8.4.2.3 Periostin
8.5 The mineralization of bone matrix
8.5.1 Nucleation and growth of mineral crystals
8.5.2 Mineral structure and interaction with the organic matrix
8.5.3 Mineral homeostasis regulation by bone cells
Acknowledgments
References
III. Skeletal hormones and regulatory factors
9 Parathyroid hormone and parathyroid hormone-related protein
9.1 Introduction
9.2 Synthesis and secretion of parathyroid hormone
9.3 Metabolism of parathyroid hormone.
9.4 Bone-resorbing action of parathyroid hormone
9.5 Effects of parathyroid hormone on bone formation
9.6 Renal actions of parathyroid hormone
9.7 Parathyroid hormone-related protein as a mediator of humoral hypercalcemia of malignancy
9.8 Physiological roles of parathyroid hormone-related protein
9.8.1 Endochondral bone development
9.8.2 Bone
9.8.3 Mammary gland
9.8.4 Skin and teeth
9.8.5 Other actions of parathyroid hormone-related protein
9.9 Mechanism of action of parathyroid hormone and parathyroid hormone-related protein
Acknowledgment
References
10 Phosphatonins
10.1 Introduction
10.2 Phosphorus homeostasis
10.2.1 Role of the kidney in phosphate homeostasis
10.2.2 Role of the intestine in phosphate homeostasis
10.3 Phosphatonins
10.4 Fibroblast growth factor 23
10.4.1 Hypophosphatemic disorders with defective mineralization
10.4.1.1 Autosomal dominant hypophosphatemic rickets
10.4.1.2 Tumor-induced osteomalacia
10.4.1.3 X-linked hypophosphatemic rickets
10.4.1.3.1 Antifibroblast growth factor 23 antibody therapy
10.4.1.4 Fibrous dysplasia/McCune Albright
10.4.2 Hyperphosphatemic disorders
10.4.2.1 Tumoral calcinosis
10.4.2.2 Chronic kidney disease
10.4.3 Effects of fibroblast growth factor 23 in the kidney and intestine
10.4.4 Fibroblast growth factor 23 and Klotho
10.4.5 Effects of fibroblast growth factor 23 in bone
10.4.6 Fibroblast growth factor 23 in normal phosphate homeostasis
10.5 Secreted frizzled-related protein 4
10.6 Matrix extracellular phosphoglycoprotein
10.7 Fibroblast growth factor 7
10.8 Summary
References
11 Skeletal growth factors
Abbreviations
11.1 Introduction
11.2 Platelet-derived growth factor
11.3 Vascular endothelial growth factor
11.4 Fibroblast growth factor.
11.5 Transforming growth factor beta.