What Is Needed for Proper Bone Development?

This book provides readers with an in-depth understanding of the pathogenesis of skeletal diseases, and is suitable for reference reading by researchers of orthopedic research institutes, clinical orthopedics and related personnel.

Human skeletal development

Chapter 1 Genetics and epigenetics of bone development 1. Introduction 2. Overview of genetic diseases of human bone development 3. Bone development 4. Gene expression during osteoblast development 5. Gene expression during osteoclast development 6. Steroid hormone receptors in bone development 7. Major genetic defects affecting bone development 8. Epigenetic regulation in development 9. Summary and conclusions Chapter 2. Tissue interactions in long bone development 1. Introduction 2. Early bone development Decisions on cell fate in medium III. Intrinsic regulation of chondrogenesis and osteogenesis 4. Interaction between cartilage and bone 5. Interaction between cartilage, bone, blood vessels and matrix ablation cells 6. Whether these tissues interact It will continue after birth. 7. Conclusions and Prospects Chapter 3. Growth plate 1. Introduction 2. Structure, layout and fusion of growth plate 3. Detailed anatomy and cell dynamics of growth plate 4. Growth plate development and function regulation 5. 5. Mechanism of growth plate mineralization 6. Metabolism of chondrocytes in growth plate 7. Removal of chondrocytes in epiphysis growth plate 8. Chondrocyte survival vs death: autologous Induced nine, ten growth plate disease, Summary Chapter 4 Hedgehog signaling pathway and a growth of a bone growth plate introduces two, three of Hedgehog signaling pathway, both human genetics and development mode Hh
Hh in bone and craniofacial development
Five, Ihh in cartilage osteogenesis
6. Hh and joint formation 7. Hh signaling in bone homeostasis Chapter 5. The role of microRNAs in skeletal development 1. Overview of micro RNA 2. Introduction to bone development and MSCs 3. Dicer enzyme inactivation model Early limb interstitial and growth Micro RNA activity in the plate 4. The role of micro RNA in bone development signaling pathways 5. The role of miRNAs in limb development Summary Chapter 6. FGF / FGFR signaling in bone dysplasia 1. Introduction 2. FGF signaling pathways in growth plates The role of FGF / FGFR signal transduction in cartilage dysplasia 4. The study of FGF signal pathways in the cranium 5. The significance of FGF / FGFR in precranial suture closure 6. Summary and conclusions Chapter 7 Hypoxia The role of inducing factors 1. Hypoxia and Hif transcription factor family 2. Relationship between Hifs and chondrocytes 3. Relationship between Hifs and osteoblasts 4. Relationship between Hifs and osteoclasts 5. Summary Chapter 8. BMP signals 1. Overview 2. BMP signal pathway 3. Mesenchymal cells aggregate and transform into BMP signals in chondrocytes 4. BMP signal pathway in chondrogenesis 5. BMP signal pathway in osteogenesis 6. BMP in adipogenesis and energy metabolism Signal Pathway 7. Prospect Chapter 9 Wnt Signaling Pathway and Bone Development I. Introduction II. The Role of LRP5 and LRP6 in Bone Formation and Development 3. The Effect of DKKS on Bone Formation and Development 4. The Effect of Kremens on Bone Formation and Development 5. The impact of SOST / sclerostin on bone formation and development 6. The impact of Wnts on bone formation and development 7. The impact of SFRPS on bone formation and development 8. The effect of downstream genes of Wnts on bone formation and development 9. Summary and conclusions Chapter 10. Development of craniofacial complex 1. Introduction 2. Craniofacial bone development 3. Mandibular development 4. Temporomandibular joint 5. Development of palate 6. Dental development 7. Prospects Chapter 11. Dentin Bone tissue: Similar to collagen mineralized tissue 1. Dental development 2. Bone formation 3. Cell lines and cell models of osteoblasts and odontoblasts 4. Transcriptional control of osteoblast and odontoblast differentiation 5. The components of the matrix in osteoblasts and odontoblasts 6. Hereditary syndromes and diseases 7. Common characteristics of bone tissue and dentin Chapter 12. Evolution of bone protein 1. On two, three gene duplication, collagen IV-hydroxy--glutamate bone proteins (osteocalcin, the BGP) protein and matrix -hydroxy-glutamic acid (the MGP)
V. Secreted calcium-bound phosphoproteins 6. Small leucine-rich proteoglycans 7. Directional evolution of apatite-binding peptides 8. Values and applications of evolutionary research 9. Conclusions Chapter 13 Osteogenesis imperfecta 1. Introduction 2. Disease taxonomy and biology 3. Clinical treatment 4. Differential diagnosis 5. Inspection of osteogenesis imperfecta 6. Biochemistry 7. Imaging 8. Histomorphometry 9. Drug therapy 10. Management of severely affected infants 10. I. Problems in adulthood 12. Prospects for the future Chapter 14. Progressive fibrous proliferative ossification: a new deformed gene for developmental understanding 1. Introduction 2. Clinical manifestations of typical FOP 3. Diagnosis and diagnosis of FOP Misdiagnosis 4. Epidemiology, genetics and environmental factors of FOP 5. FOP and BMP signaling pathway 6. FOP gene 7. Atypical FOP phenotype caused by new mutations in FOP gene 8. Protein homology spectrum of FOP gene 9. FOP and morphogenesis X. FOP and deformation XII. FOP and canceration XII. FOP and degenerative joint disease XIII. Prevention and treatment of bone deformation in patients with FOP XIV. Conclusion Chapter 15 Bone salt balance and related pathology 2. Overview 2. Physiological characteristics of bone salt balance 3. Pathological characteristics of bone salt balance 4. Pathogenesis of diseases related to vitamin D and calcium deficiency 5. Conclusion Chapter 16 Intrinsic connections between bone and other tissues: brain-bone axis and Bone-Adipose Tissue Axis 1. Overview 2. Leptin and Bone 3. Regulation of Leptin on Bone Reconstruction 4. Leptin and Bone Reconstruction in Human Body 5. Leptin, Sympathetic Nervous System and Bone Reconstruction 6. Sympathetic Nervous System and Bone Reconstruction: Clinical Implications 7. Regulation of Bone Reconstruction by Neuropeptides Affecting Appetite: Cart and MC4R
Eight, melanocortin 4 receptors Nine, neuromodulin U
Ten, Npy
11. Regulation of glucose metabolism in skeletal cells 12. Osteocalcin as a potential treatment method for diabetes 13. Leptin regulates glucose metabolism through osteoblasts through the sympathetic nervous system 14. Clinical significance of bone regulation of glucose metabolism 15. Summary Chapter 17. Mechanical Biology and Computational Simulation of Bone Development 1. Bone Function and Morphology 2. Mechanical Biology Regulation and Simulation of Bone Growth 3. Mechanical Biology Regulation and Reconstruction Simulation of Bone Reconstruction 4. Mechanical Biology of Fracture Healing Tuning and simulation

This book is the sixth volume in the "Bone Biology Topics" series, which mainly explains the process of bone formation from growth to mineralization. Understanding the process of tissue generation requires combining information from embryology and histology with molecular and genetic knowledge. At each stage of development, some genes are expressed and others are silent. Diseases, especially the progression of the disease, are also characterized by changes in gene expression that are passed on to progeny cells. In both cases, the regulation of gene expression and its partial or complete silencing is often the result of interactions between the genome and the epigenome, like the relationship between a very stable structure and rapidly changing environmental factors.
Chapter 1 by OConnor, Farach-Carson, and Schanen is an overview of the field and topics that will be discussed in more detail in subsequent chapters. After discussing osteogenesis in terms of intramembranous and intrachondral osteogenesis, this chapter describes the gene expression in osteoblasts and osteoclasts, the cross-linking effect of osteocytes and the regulation of steroid hormones. The major genetic defects that cause a variety of orthopedic diseases-Marfan syndrome, Pater's disease, and adolescent osteoporosis were analyzed. This chapter concludes with the epigenetic regulation of osteogenesis, including methylation, histone modification, and imprinting. This chapter, like other chapters, has a wealth of literature pictures to illustrate the basic points.
In Chapter 2, Colnot and Alliston describe the complex interactions of cells and molecules in controlling bone stereotypes and morphogenesis during embryonic development. This chapter first describes the differentiation, interaction of chondrocytes and osteoblasts, and the regulation of perichondrium. It then proceeds to signalling pathways that describe perichondrial maturation and perichondrial cell recruitment into synthetic stromal osteoblasts. The authors discussed the role of angiogenesis and absorption of stromal cells and raised questions about the continued interaction of tissues after birth. At the end they called for attention to animal models and genetic methods.
In Chapter 3, the complex structures that make up the epiphyseal growth plate are discussed and written by Anderson and Shapiro. They described the structure of the growth plate, detailed anatomy and cell dynamics, the role of many regulatory factors such as parathyroid hormone-related proteins, thyroxine, glucocorticoids, and leptin, and analyzed the mineralization process in detail. Chondrocytes play an important metabolic role on the growth plate, but they are eventually cleared from the organ. This process occurs either through apoptosis induced by an endogenous pathway regulated by part of the Bcl-2 gene family, or by cell death induced by an exogenous pathway acting as a cell death ligand receptor. On the other hand, autophagy can also cause degradation of cellular components. The last part of this chapter discusses a number of diseases, including rickets, chondrogenesis, and endogenous chondroma.
The Hedgehog protein signaling pathway found in Drosophila and highly conserved in humans affects cell behavior, including proliferation, differentiation, and survival. In Chapter 4, Regard, Mak, Gordon, and Yang describe the effects of two of the three genes that make up the vertebrate Hedgehog protein family: the Sonic Hedgehog protein, the Indian Hedgehog protein, and the Desert Hedgehog protein. The expression of the latter is limited. In the gonads. This chapter details the Hedgehog protein signaling pathway and its role in human genetics and skeletal development, including craniofacial development. The authors also described the role of Sonic Hedgehog protein, especially in finger (toe) formation and limb growth, and pointed out that Sonic Hedgehog protein is a major regulator of early embryogenesis and craniofacial morphogenesis, while Indian Hedgehog protein is A key regulator of cartilage osteogenesis and ossification. This chapter concludes by discussing the role of Hedgehog proteins in joint formation and bone homeostasis.
Micro RNA constitutes the most abundant type of regulation in post-transcriptional regulation of the genome. They play an important role in development and differentiation. In Chapter 5, Gradus and Hornstein summarize the biological basis of these molecules and evidence that micro RNA is an essential component of the gene profile that controls bone and limb development. Micro RNA is involved in the Hedgehog protein pathway, and as the authors have discussed, specific micro RNA214 is regulated by the transcription factor Twist, and its deficiency can lead to the Sercoli syndrome. Micro RNA is related to bone morphogenetic protein and fibroblast growth factor signaling, and cartilage-specific micro RNA140 regulates platelet-derived growth factor. Finally, the authors point out that increasing understanding of these molecular regulatory effects will give us a better understanding of development and diseases caused by mutations in micro RNA expression.
In Chapter 6, Pierre J. Marie discusses the fibroblast growth factor / fibroblast growth factor receptor signaling pathway in detail. Including the pathway in the growth plate, cartilage hypoplasia and mutations that trigger these diseases. In the skull, fibroblast growth factor signaling up-regulates osteogenesis, and missense mutations in its receptors lead to premature cranial suture fusion and many skeletal disorders, including Apert-Crouzon syndrome. Marie concluded that there is a need to study genes induced by fibroblast growth factor receptor signaling and genes involved in the pathogenesis of dysplasia.
Until the circulatory system is established, embryo development continues under hypoxic conditions. In Chapter 7, Schipani and Khatri discuss hypoxia-inducible factor 1 as the primary regulatory transcription factor for cells to adapt to hypoxia. Hypoxia-inducible factor 1 can act on two other factors that sense changes in oxygen pressure. The authors discussed their interactions and other target genes for hypoxia-inducible factor 1 and their relationships with energy metabolism, angiogenesis, and autophagy. Further discussion is about its relationship with chondrocyte survival, proliferation, and differentiation. Hypoxia-inducible factor 1 also plays a role in joint development, articular cartilage, and osteoblasts, osteoclasts, and bone formation and reconstruction that we have previously analyzed.
Bone morphogenetic protein was discovered more than 40 years ago, but it has only been identified and purified later, and it plays a major role in the development mode, tooth development, and regulation of autophagy. In Chapter 8, Estrada and Lyons describe the signaling pathways of these proteins, their role in directing chondrogenesis to mesenchymal aggregation, and the expression of bone morphogenetic proteins on the transcription factor Sox9 expressed in all cartilage primordia. And dialogic links with other signaling pathways such as the Indian Hedgehog protein, parathyroid hormone-related protein, and fibroblast growth factor. These proteins also play a signaling role in osteogenesis and regulating the RANKL-osteoprotectin pathway. The authors point out that the classic bone morphogenetic protein signaling pathway is involved in the regulation of the transcription factor Runx2, adipogenesis, and energy metabolism.
In Chapter 9, Bodine describes another important signaling pathway, the Wnt signaling pathway, which is a large family of polypeptides that play key signaling roles in embryogenesis, organogenesis, and morphogenesis. This chapter describes the loss and acquisition of LRP5 functional mutations as human Wnt co-receptors, and then continues to explain the expression of Dickkopf in osteoblast function and bone formation. Bodine analyzed the effect of SOST / osteoostin, which can block signals through bone morphogenetic proteins and Wnt. Apparently, osteostein inhibits bone formation by inactivating the classical Wnt pathway. This chapter describes the effects of several Wnt proteins, Dickkopf factors, and secreted curl-related proteins on bone formation and development. In addition, the status of -catenin and T cell-specific transcription factors produced by adenoma-like polyp genes in skeletal development was also discussed.
The craniofacial complex, including the head, face, and mouth, highlights personal characteristics and is therefore the most unique part of the human body. In Chapter 10, D Souza, Ruest, Hinton, and Svoboda detail the structure of this complex and the development of its constituent parts. Starting from the genes and signaling pathways involved, they described the development of the mandible, its molecular regulation, and the developmental pattern of mandibular neural crest cells. Later, this chapter describes the temporomandibular joint, including morphogenesis, postnatal growth, and maturation. Next, the morphogenesis and molecular mechanism of epiphyseal development are discussed, with emphasis on a variety of signal pathways; subsequently, the ossification and epiphyseal deformity of epiphysis are also analyzed. The last part is about the role of tooth development, signal interaction and extracellular matrix in tooth morphogenesis and cell differentiation.
In Chapter 11, MacDougall and Javed complete the previous chapter and compare the dentin and bone mineralization processes. After the first and second discussions on tooth development and dentinogenesis, this chapter describes and compares the cell differentiation of osteoblasts and odontoblasts, and analyzes the differentiation and regulatory transcription by growth factors and hormones Regulation, the effect of mechanism factors. Finally, a discussion of reconstruction, repair, genetic syndromes, and diseases is concluded by comparing bone and dentin.
In Chapter 12, Wang and Lee discuss the evolution of bone protein. The focus is on genes for extracellular matrix proteins, many of which are specific to mineralized tissues and have no analogs in non-mineralized organism tissues. After reviewing the process of gene replication, the authors discussed the evolutionary connections between collagen, osteocalcin, matrix Gla protein, and the importance of higher organism development. Later, this chapter discusses the secretion of calcium-binding proteins. They have only limited sequence homology, but their genetic structure and biochemical characteristics determine their evolutionary relationship. Other topics discussed include the evolution of small leucine-rich proteoglycans and apatite-binding peptides. The evolution of bone formation and ossification is evaluated at the end of this chapter.
Osteogenesis imperfecta is a genetic disorder that occurs in about 0.02% of newborns and can cause premature dysplasia. Survivors have fragile bones. In Chapter 13, Arundel and Bishop discuss the biology of the disease, its animal models, and the osteomalacia it causes, then detail the clinical treatments. The author discusses the patient's medical history and physical examination, including dental manifestations, differential diagnosis, and examination of the disease. These include biochemical analysis, radiography, and histomorphometry. Assess the effects of calcitonin, growth hormone, and bisphosphate, and analyze problems that occur in adults, namely hearing impairment, cardiovascular disease, and respiratory disease.
In Chapter 14, Kaplan, Groppe, Seemann, Pignolo, and Shore discuss progressive ossifying fibrodysplasia, which is an anti-complex missense of a receptor for bone morphogenetic protein, the type I receptor Caused by the mutation. The mutation causes abnormal bone morphological development and tissue damage, deformation of bone connective tissue, degenerative joint disease, and benign bone tumors. This chapter describes the clinical and molecular characteristics, diagnosis and misdiagnosis, signaling pathways and genes of the disease, and then discusses the abnormalities of morphogenesis, deformation, tumor formation, and joint function caused by this morphological gene. Progressive ossifying fibrous dysplasia has neither mature therapies nor cures, but the authors discuss feasible options such as intervening in signaling pathways or blocking the initiation of inflammation.
Bone mineral homeostasis comes from the interaction of vitamin D and the parathyroid hormone regulatory system. In Chapter 15, Peterlik details from a molecular perspective how 1,25-dihydroxyvitamin D3 and extracellular calcium ions act as co-regulators to regulate cell proliferation, differentiation and function in many organs and cell systems Effect, and how bone homeostasis during development is maintained by the synergistic action of parathyroid hormone and parathyroid hormone-related proteins. After birth, the vitamin D endocrine system strongly intervenes in this process through the 25-hydroxy-D3-24-hydroxylase encoded by CYP24A1. Peterlik discusses the short- and long-term dysfunction of mineral metabolism, focusing on vitamin D status and calcium intake. He then analyzed rickets and osteomalacia, osteoporosis, cancer, type 1 diabetes (insulin-dependent diabetes mellitus), hypertension, chronic effects on the role of two endocrine regulatory systems and their effects on calcium receptors on the cell membrane. Vascular disease and chronic kidney disease.
In Chapter 16, Takeda called for attention to the important relationships between bone and energy and sugar metabolism that are now recognized. He discussed the role of leptin in regulating bone mass and bone remodeling, noting that animal experiments have shown that leptin has significantly different effects on appetite and bone metabolism, the latter being mediated by leptin receptors in the ventromedial hypothalamus. . This suggests the role of the sympathetic nervous system. The effects of neuropeptide, neuromedin, melacortin, neuropeptide and their interrelationships on bone mass, which affect appetite, are then discussed. The last section of this chapter is devoted to explaining the regulation of glucose metabolism and osteocalcin in bone cells.
With sufficient information, it becomes possible to mimic a system and to prove the correlation through experiments. Chen, Schuetz, and Pearcy describe and simulate the biodynamic regulation of bone growth, reconstruction, and fracture healing in Chapter 17. They describe the function and form of bone and provide an equation that relates stress to bending time / bending resistance score by multiplying the outer diameter of the bone. This is not just a model, it can also predict that if the area remains the same, if the inner diameter increases, the stress will decrease. Based on the available evidence, the authors proposed the concept of osteogenesis index, and proposed formulas to define distortion stress and hydrostatic stress. If bone density is considered a characteristic of the internal structure, then the reconstruction of reticular and cortical bone can be described. The last part of this chapter deals with fracture healing and publications with recommended models for fracture healing.
This book, like the previous books in this series, reflects the conceptual interlinkages between medical science and medical practice, and how effective practice benefits from the advancement of knowledge. It also allows us to understand that we have a complete understanding of skeleton And how far is its function as an organ system. We thank all authors for their contributions to their respective themes and for having this opportunity to integrate this large and exciting knowledge. We are grateful to our publisher Springer for its help in ensuring intellectual and aesthetic qualities.