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==Introduction==
 
==Introduction==
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'''Osteogenesis''' is the formation of [[Bones and Cartilage - Anatomy & Physiology#Types of Bone|bone]]. Bone forms from one of three lineages; the skull forms from the [[Neurogenesis - Anatomy & Physiology#Neural Crest|'''neural crest''']]; the limb skeleton forms from the '''lateral plate mesoderm'''; and the axial skeleton forms from the '''paraxial mesoderm (sclerotome)'''. There are two methods of osteogenesis. Both involve the transformation of the pre - existing mesenchymal tissue into bone.
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1. '''Intramembranous Ossification''' - the direct conversion of mesenchymal tissue into bone. Occurs in production of the skull.
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2. '''Endochondrial Ossification''' - the mesechymal tissue first differentiates into [[Bones and Cartilage - Anatomy & Physiology#Structure and Function of Cartilage|cartilage]], then into bone. This occurs in the production of the limb and axial skeleton. Limb cartilage is produced in a proximal to distal direction as a continuous structure. It becomes punctuated with [[Developmental Biology Overview - Anatomy & Physiology#Joints|joints]] later, and then converted to bone.
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==Endochondrial Ossification==
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Bone formation via [[Bones and Cartilage - Anatomy & Physiology#Structure and Function of Cartilage|cartilage]] occurs in the following stages:
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1. The proliferating limb mesenchyme condenses.
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2. The increased cell density triggers mesenchymal cells to differentiate into chondrocytes. Proliferation continues and the bone shape is formed, with a diaphysis (shaft) and epiphysis (bulbous ends).
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3. Chondrocytes in the middle of the diaphysis stop proliferating and undergo '''hypertrophy'''. The shaft is surrounded by the '''perichondrium''', a restrictive membrane. This means that the bone can only grow in length, not width. The epiphyses are pushed away from each other.
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4. After the chondrocytes have undergone hypertrophy, they die.
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5. '''Osteoblasts''' on the inner side of the perichondrium invade the cartilage matrix. They then secrete the extra - cellular matrix, characteristic of bone.
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6. Ossification occurs from the outside in. This is called '''primary ossification''', or perichondrial ossification. Blood vessels invade the central region of the diaphysis to transport [[Bone Marrow - Anatomy & Physiology|bone marrow]] stem cells and osteoclasts. The osteoclasts break down the cartilage matrix to allow room for the bone marrow.
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There is no perichondrium surrounding the epiphysis, this allows for expansion in length of the bone, but means that there are no surrounding osteoblasts to invade. To achieve osteogenesis, blood vessels invade from the diaphysis and carry osteoblasts with them. In the epiphysis, osteoblasts initiate bone growth from the inside out. This is called '''secondary ossification'''. In some mammals, secondary ossification occurs after birth. The bone becomes covered in a layer containing osteoblasts.
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Cartilage is ''not replaced by bone'' in two areas:
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# In between the diaphysis and epiphysis, a region called the '''epiphyseal growth plate (EPG)'''.
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# At the ends of the epiphysis, between the joints. Acts as a '''shock absorber'''.
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==Development of Bone and Cartilage==
      
'''Osteogenesis''' is the formation of [[Bones and Cartilage - Anatomy & Physiology#Types of Bone|bone]]. Bone forms from one of three lineages; the skull forms from the [[Neurogenesis - Anatomy & Physiology#Neural Crest|'''neural crest''']]; the limb skeleton forms from the '''lateral plate mesoderm'''; and the axial skeleton forms from the '''paraxial mesoderm (sclerotome)'''.  
 
'''Osteogenesis''' is the formation of [[Bones and Cartilage - Anatomy & Physiology#Types of Bone|bone]]. Bone forms from one of three lineages; the skull forms from the [[Neurogenesis - Anatomy & Physiology#Neural Crest|'''neural crest''']]; the limb skeleton forms from the '''lateral plate mesoderm'''; and the axial skeleton forms from the '''paraxial mesoderm (sclerotome)'''.  
 
There are two methods of osteogenesis;
 
There are two methods of osteogenesis;
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1. '''Intramembranous Ossification'''
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===1. Intramembranous Ossification===
    
Forms the '''flat''' bones of skull and mandible. There is no cartilaginous precursor, the mesenchyme forms bone directly. The mesenchyme condenses, differentiates to pre-osteoblasts, then to osteoblasts. The osteoblasts synthesize osteoid (collagen and proteoglycans) causing mineralization and bone spicule formation. Spicules produce spongy bone. The bone growth can be described as appositional growth, where bone is laid down on the exterior (vs interior) surface of the developing bone. During bone development there is an increasing association with blood vessels and bone marrow is formed by the mesenchyme, between the bone and the blood vessels.
 
Forms the '''flat''' bones of skull and mandible. There is no cartilaginous precursor, the mesenchyme forms bone directly. The mesenchyme condenses, differentiates to pre-osteoblasts, then to osteoblasts. The osteoblasts synthesize osteoid (collagen and proteoglycans) causing mineralization and bone spicule formation. Spicules produce spongy bone. The bone growth can be described as appositional growth, where bone is laid down on the exterior (vs interior) surface of the developing bone. During bone development there is an increasing association with blood vessels and bone marrow is formed by the mesenchyme, between the bone and the blood vessels.
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2. '''Endochondral Ossification'''
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===2. Endochondral Ossification===
    
This is responsible for embryonic bone formation, as well as the growth in length. This occurs via a cartilaginous precursor. The mesenchyme condenses to form the bone outline. The increased cell density triggers core cells to differentiate to chondrocytes and begin secreting the cartilage matrix. Proliferation continues and the bone shape is formed, with a diaphysis (shaft) and epiphysis (bulbous ends). Chondrocytes in the middle of the diaphysis stop proliferating and undergo '''hypertrophy'''. The shaft is surrounded by the '''perichondrium''', a restrictive membrane. This means that the bone can only grow in length, not width. The epiphyses are pushed away from each other. After the chondrocytes have undergone hypertrophy, they die. '''Osteoblasts''' on the inner side of the perichondrium invade the cartilage matrix. They then secrete the extra - cellular matrix, characteristic of bone. Ossification occurs from the outside in. This is called '''primary ossification''', or perichondrial ossification. Blood vessels invade the central region of the diaphysis to transport [[Bone Marrow - Anatomy & Physiology|bone marrow]] stem cells and osteoclasts. The osteoclasts break down the cartilage matrix to allow room for the bone marrow.
 
This is responsible for embryonic bone formation, as well as the growth in length. This occurs via a cartilaginous precursor. The mesenchyme condenses to form the bone outline. The increased cell density triggers core cells to differentiate to chondrocytes and begin secreting the cartilage matrix. Proliferation continues and the bone shape is formed, with a diaphysis (shaft) and epiphysis (bulbous ends). Chondrocytes in the middle of the diaphysis stop proliferating and undergo '''hypertrophy'''. The shaft is surrounded by the '''perichondrium''', a restrictive membrane. This means that the bone can only grow in length, not width. The epiphyses are pushed away from each other. After the chondrocytes have undergone hypertrophy, they die. '''Osteoblasts''' on the inner side of the perichondrium invade the cartilage matrix. They then secrete the extra - cellular matrix, characteristic of bone. Ossification occurs from the outside in. This is called '''primary ossification''', or perichondrial ossification. Blood vessels invade the central region of the diaphysis to transport [[Bone Marrow - Anatomy & Physiology|bone marrow]] stem cells and osteoclasts. The osteoclasts break down the cartilage matrix to allow room for the bone marrow.
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Cartilage is ''not replaced by bone'' in two areas:
 
Cartilage is ''not replaced by bone'' in two areas:
1. In between the diaphysis and epiphysis, a region called the '''epiphyseal growth plate (EPG)'''.
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1. In between the diaphysis and epiphysis, a region called the '''epiphyseal growth plate (EGP)'''.
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2. At the ends of the epiphysis, between the joints. Acts as a '''shock absorber'''.
 
2. At the ends of the epiphysis, between the joints. Acts as a '''shock absorber'''.
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==Bone Growth==
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===Length===
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The '''epiphyseal growth plate (EPG)''' allows the [[Bones and Cartilage - Anatomy & Physiology#Types of Bone|bone]] to continue to grow in length after birth. The EPG is a region of continuous chondroblast differentiation and maturation and can be divided into five zones:
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# '''Germinal Zone''' - chondroblast division at a low rate, and self renewal.
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# '''Proliferation Zone''' - chondroblast division at a fast rate.
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# '''Maturation Zone''' - chondroblast differentiation into chondrocytes.
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# '''Hypertrophic Zone''' - chondrocytes enlarge and then die.
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# '''Dead cells''' become the matrix for bone growth.
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===Girth===
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The '''periosteum''' lines the outer surface of the diaphysis of the bone. It has a cellular inner layer, consisting of osteoblasts, and a fibrous outer layer. The '''endosteum''' lines the inner surface of the diaphysis of the bone. It contains osteoblasts ''and'' osteoclasts. Bone growth occurs by a shift in the equilibrium between osteoblasts and osteoclasts. Osteoblasts on the outside in the periosteum add bone to increase the bone's diameter. Osteoclasts on the inside in the endosteum remove this bone to maintain the bone diameter. When osteoclasts start removing less bone, or osteoblasts start adding more bone, the girth increases.
            
[[Category:Developmental Biology]][[Category:Bone and Cartilage - Anatomy & Physiology]]
 
[[Category:Developmental Biology]][[Category:Bone and Cartilage - Anatomy & Physiology]]
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