In the bone lengthening process during endochondral ossification depends on the growth of epiphyseal cartilage. When the epiphyseal line has been closed, the bone will not increase in length. Unlike bone, cartilage bone growth is based on apposition and interstitial growth. In areas where cartilage bone is covered by bone, various variations of zone characteristics, based on the developmental stages of each individual, can differentiate which then continuously merge with each other during the conversion process.
Environmental influences co: mechanism of orthopedic functional tools have a strong effect on condylar cartilage because the bone is located more superficially [ 5 ].
Cartilage bone height development occurs during the third month of intra uterine life. Cartilage plate extends from the nasal bone capsule posteriorly to the foramen magnum at the base of the skull. It should be noted that cartilages which close to avascular tissue have internal cells obtained from the diffusion process from the outermost layer. This means that the cartilage must be flatter.
In the early stages of development, the size of a very small embryo can form a chondroskeleton easily in which the further growth preparation occurs without internal blood supply [ 1 ]. During the fourth month in the uterus, the development of vascular elements to various points of the chondrocranium and other parts of the early cartilage skeleton becomes an ossification center, where the cartilage changes into an ossification center, and bone forms around the cartilage.
Cartilage continues to grow rapidly but it is replaced by bone, resulting in the rapid increase of bone amount. Finally, the old chondrocranium amount will decrease in the area of cartilage and large portions of bone, assumed to be typical in ethmoid, sphenoid, and basioccipital bones. The cartilage growth in relation to skeletal bone is similar as the growth of the limbs [ 1 , 3 ]. Longitudinal bone growth is accompanied by remodeling which includes appositional growth to thicken the bone.
This process consists of bone formation and reabsorption. Bone growth stops around the age of 21 for males and the age of 18 for females when the epiphyses and diaphysis have fused epiphyseal plate closure. Normal bone growth is dependent on proper dietary intake of protein, minerals and vitamins. A deficiency of vitamin D prevents calcium absorption from the GI tract resulting in rickets children or osteomalacia adults. Osteoid is produced but calcium salts are not deposited, so bones soften and weaken.
At the length of the long bones, the reinforcement plane appears in the middle and at the end of the bone, finally produces the central axis that is called the diaphysis and the bony cap at the end of the bone is called the epiphysis. Between epiphyses and diaphysis is a calcified area that is not calcified called the epiphyseal plate.
Epiphyseal plate of the long bone cartilage is a major center for growth, and in fact, this cartilage is responsible for almost all the long growths of the bones. This is a layer of hyaline cartilage where ossification occurs in immature bones. On the epiphyseal side of the epiphyseal plate, the cartilage is formed. On the diaphyseal side, cartilage is ossified, and the diaphysis then grows in length.
The epiphyseal plate is composed of five zones of cells and activity [ 3 , 4 ]. Near the outer end of each epiphyseal plate is the active zone dividing the cartilage cells.
Some of them, pushed toward diaphysis with proliferative activity, develop hypertrophy, secrete an extracellular matrix, and finally the matrix begins to fill with minerals and then is quickly replaced by bone. As long as cartilage cells multiply growth will continue. Finally, toward the end of the normal growth period, the rate of maturation exceeds the proliferation level, the latter of the cartilage is replaced by bone, and the epiphyseal plate disappears. At that time, bone growth is complete, except for surface changes in thickness, which can be produced by the periosteum [ 4 ].
Bones continue to grow in length until early adulthood. The lengthening is stopped in the end of adolescence which chondrocytes stop mitosis and plate thins out and replaced by bone, then diaphysis and epiphyses fuse to be one bone Figure 7.
The rate of growth is controlled by hormones. When the chondrocytes in the epiphyseal plate cease their proliferation and bone replaces the cartilage, longitudinal growth stops. All that remains of the epiphyseal plate is the epiphyseal line. Epiphyseal plate closure will occur in year old females or year old males. Oppositional bone growth and remodeling. The epiphyseal plate is responsible for longitudinal bone growth. The cartilage found in the epiphyseal gap has a defined hierarchical structure, directly beneath the secondary ossification center of the epiphysis.
By close examination of the epiphyseal plate, it appears to be divided into five zones starting from the epiphysis side Figure 8 [ 4 ]: The resting zone: it contains hyaline cartilage with few chondrocytes, which means no morphological changes in the cells.
The proliferative zone: chondrocytes with a higher number of cells divide rapidly and form columns of stacked cells parallel to the long axis of the bone. The hypertrophic cartilage zone: it contains large chondrocytes with cells increasing in volume and modifying the matrix, effectively elongating bone whose cytoplasm has accumulated glycogen. The resorbed matrix is reduced to thin septa between the chondrocytes. The calcified cartilage zone: chondrocytes undergo apoptosis, the thin septa of cartilage matrix become calcified.
The ossification zone: endochondral bone tissue appears. Blood capillaries and osteoprogenitor cells from the periosteum invade the cavities left by the chondrocytes. The osteoprogenitor cells form osteoblasts, which deposit bone matrix over the three-dimensional calcified cartilage matrix. Epiphyseal plate growth. Five zones of epiphyseal growth plate includes: 1. When bones are increasing in length, they are also increasing in diameter; diameter growth can continue even after longitudinal growth stops.
This is called appositional growth. The bone is absorbed on the endosteal surface and added to the periosteal surface. Osteoblasts and osteoclasts play an essential role in appositional bone growth where osteoblasts secrete a bone matrix to the external bone surface from diaphysis, while osteoclasts on the diaphysis endosteal surface remove bone from the internal surface of diaphysis.
The more bone around the medullary cavity is destroyed, the more yellow marrow moves into empty space and fills space. Osteoclasts resorb the old bone lining the medullary cavity, while osteoblasts through intramembrane ossification produce new bone tissue beneath the periosteum. Periosteum on the bone surface also plays an important role in increasing thickness and in reshaping the external contour.
The erosion of old bone along the medullary cavity and new bone deposition under the periosteum not only increases the diameter of the diaphysis but also increases the diameter of the medullary cavity. This process is called modeling Figure 9 [ 3 , 4 , 15 ].
Appositional bone growth. Bone deposit by osteoblast as bone resorption by osteoclast. Recent research reported that bone microstructure is also the principle of bone function, which regulates its mechanical function.
Bone tissue function influenced by many factors, such as hormones, growth factors, and mechanical loading. The microstructure of bone tissue is distribution and alignment of biological apatite BAp crystallites. This is determined by the direction of bone cell behavior, for example cell migration and cell regulation.
Ozasa et al. Generally, bone is formed by endochondral or intramembranous ossification. Intramembranous ossification is essential in the bone such as skull, facial bones, and pelvis which MSCs directly differentiate to osteoblasts. While, endochondral ossification plays an important role in most bones in the human skeleton, including long, short, and irregular bones, which MSCs firstly experience to condensate and then differentiate into chondrocytes to form the cartilage growth plate and the growth plate is then gradually replaced by new bone tissue [ 3 , 8 , 12 ].
MSC migration and differentiation are two important physiological processes in bone formation. MSCs migration raise as an essential step of bone formation because MSCs initially need to migrate to the bone surface and then contribute in bone formation process, although MSCs differentiation into osteogenic cells is also crucial.
MSC migration during bone formation has attracted more attention. Some studies show that MSC migration to the bone surface is crucial for bone formation [ 17 ]. Bone marrow and periosteum are the main sources of MSCs that participate in bone formation [ 18 ]. In the intramembranous ossification, MSCs undergo proliferation and differentiation along the osteoblastic lineage to form bone directly without first forming cartilage.
MSC and preosteoblast migration is involved in this process and are mediated by plentiful factors in vivo and in vitro. MSCs initially differentiate into preosteoblasts which proliferate near the bone surface and secrete ALP. Then they become mature osteoblasts and then form osteocytes which embedded in an extracellular matrix ECM.
In the endochondral ossification, MSCs are first condensed to initiate cartilage model formation. During condensation, the central part of MSCs differentiates into chondrocytes and secretes cartilage matrix. While, other cells in the periphery, form the perichondrium that continues expressing type I collagen and other important factors, such as proteoglycans and ALP.
Chondrocytes undergo rapid proliferation. Chondrocytes in the center become maturation, accompanied with an invasion of hypertrophic cartilage by the vasculature, followed by differentiation of osteoblasts within the perichondrium and marrow cavity.
The inner perichondrium cells differentiate into osteoblasts, which secrete bone matrix to form the bone collar after vascularization in the hypertrophic cartilage. During bone formation, woven bone haphazard arrangement of collagen fibers is remodeled into lamellar bones parallel bundles of collagen in a layer known as lamellae. Periosteum is a connective tissue layer on the outer surface of the bone; the endosteum is a thin layer generally only one layer of cell that coats all the internal surfaces of the bone.
Major cell of bone include: osteoblasts from osteoprogenitor cells, forming osteoid that allow matrix mineralization to occur , osteocytes from osteoblasts; closed to lacunae and retaining the matrix and osteoclasts from hemopoietic lineages; locally erodes matrix during bone formation and remodeling. Intramembranous bone formation occurs when bone forms inside the mesenchymal membrane.
Bone tissue is directly laid on primitive connective tissue referred to mesenchyma without intermediate cartilage involvement. It forms bone of the skull and jaw; especially only occurs during development as well as the fracture repair.
Endochondral bone formation occurs when hyaline cartilage is used as a precursor to bone formation, then bone replaces hyaline cartilage, forms and grows all other bones, occurs during development and throughout life. During interstitial epiphyseal growth elongation of the bone , the growth plate with zonal organization of endochondral ossification, allows bone to lengthen without epiphyseal growth plates enlarging zones include:.
During appositional growth, osteoclasts resorb old bone that lines the medullary cavity, while osteoblasts, via intramembranous ossification, produce new bone tissue beneath the periosteum. Mesenchymal stem cell migration and differentiation are two important physiological processes in bone formation.
The author is grateful to Zahrona Kusuma Dewi for assistance with preparation of the manuscript. The authors declare that there is no conflict of interests regarding the publication of this paper. Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution 3. Help us write another book on this subject and reach those readers.
Login to your personal dashboard for more detailed statistics on your publications. Edited by Haisheng Yang. Before this time, the embryonic skeleton consists entirely of fibrous membranes and hyaline cartilage. The development of bone from fibrous membranes is called intramembranous ossification; development from hyaline cartilage is called endochondral ossification.
Bone growth continues until approximately age Bones can grow in thickness throughout life, but after age 25, ossification functions primarily in bone remodeling and repair. Intramembranous ossification is the process of bone development from fibrous membranes.
It is involved in the formation of the flat bones of the skull, the mandible, and the clavicles. Ossification begins as mesenchymal cells form a template of the future bone.
They then differentiate into osteoblasts at the ossification center. Osteoblasts secrete the extracellular matrix and deposit calcium, which hardens the matrix. The non-mineralized portion of the bone or osteoid continues to form around blood vessels, forming spongy bone. Connective tissue in the matrix differentiates into red bone marrow in the fetus. The spongy bone is remodeled into a thin layer of compact bone on the surface of the spongy bone.
Endochondral ossification is the process of bone development from hyaline cartilage. All of the bones of the body, except for the flat bones of the skull, mandible, and clavicles, are formed through endochondral ossification. In long bones, chondrocytes form a template of the hyaline cartilage diaphysis. Responding to complex developmental signals, the matrix begins to calcify.
This calcification prevents diffusion of nutrients into the matrix, resulting in chondrocytes dying and the opening up of cavities in the diaphysis cartilage. Blood vessels invade the cavities, and osteoblasts and osteoclasts modify the calcified cartilage matrix into spongy bone.
Osteoclasts then break down some of the spongy bone to create a marrow, or medullary, cavity in the center of the diaphysis. Dense, irregular connective tissue forms a sheath periosteum around the bones. The periosteum assists in attaching the bone to surrounding tissues, tendons, and ligaments. The bone continues to grow and elongate as the cartilage cells at the epiphyses divide.
In the last stage of prenatal bone development, the centers of the epiphyses begin to calcify. Secondary ossification centers form in the epiphyses as blood vessels and osteoblasts enter these areas and convert hyaline cartilage into spongy bone.
Until adolescence, hyaline cartilage persists at the epiphyseal plate growth plate , which is the region between the diaphysis and epiphysis that is responsible for the lengthwise growth of long bones Figure 1.
Figure 1. The periosteum is the connective tissue on the outside of bone that acts as the interface between bone, blood vessels, tendons, and ligaments. Without cartilage inhibiting blood vessel invasion, blood vessels penetrate the resulting spaces, not only enlarging the cavities but also carrying osteogenic cells with them, many of which will become osteoblasts.
These enlarging spaces eventually combine to become the medullary cavity. Bone is now deposited within the structure creating the primary ossification center Figure 6. This continued growth is accompanied by remodeling inside the medullary cavity osteoclasts were also brought with invading blood vessels and overall lengthening of the structure Figure 6. By the time the fetal skeleton is fully formed, cartilage remains at the epiphyses and at the joint surface as articular cartilage.
After birth, this same sequence of events matrix mineralization, death of chondrocytes, invasion of blood vessels from the periosteum, and seeding with osteogenic cells that become osteoblasts occurs in the epiphyseal regions, and each of these centers of activity is referred to as a secondary ossification center Figure 6. Throughout childhood and adolescence, there remains a thin plate of hyaline cartilage between the diaphysis and epiphysis known as the growth or epiphyseal plate Figure 6.
Eventually, this hyaline cartilage will be removed and replaced by bone to become the epiphyseal line. The epiphyseal plate is the area of elongation in a long bone. It includes a layer of hyaline cartilage where ossification can continue to occur in immature bones. We can divide the epiphyseal plate into a diaphyseal side closer to the diaphysis and an epiphyseal side closer to the epiphysis.
On the epiphyseal side of the epiphyseal plate, hyaline cartilage cells are active and are dividing and producing hyaline cartilage matrix. On the diaphyseal side of the growth plate, cartilage calcifies and dies, then is replaced by bone figure 6.
As cartilage grows, the entire structure grows in length and then is turned into bone. Once cartilage cannot grow further, the structure cannot elongate more.
The epiphyseal plate is composed of five zones of cells and activity Figure 6. The reserve zone is the region closest to the epiphyseal end of the plate and contains small chondrocytes within the matrix.
These chondrocytes do not participate in bone growth but secure the epiphyseal plate to the overlying osseous tissue of the epiphysis.
The proliferative zone is the next layer toward the diaphysis and contains stacks of slightly larger chondrocytes. It makes new chondrocytes via mitosis to replace those that die at the diaphyseal end of the plate. Chondrocytes in the next layer, the zone of maturation and hypertrophy , are older and larger than those in the proliferative zone.
The more mature cells are situated closer to the diaphyseal end of the plate. The longitudinal growth of bone is a result of cellular division in the proliferative zone and the maturation of cells in the zone of maturation and hypertrophy.
This growth within a tissue is called interstitial growth. Most of the chondrocytes in the zone of calcified matrix , the zone closest to the diaphysis, are dead because the matrix around them has calcified, restricting nutrient diffusion. Capillaries and osteoblasts from the diaphysis penetrate this zone, and the osteoblasts secrete bone tissue on the remaining calcified cartilage.
Thus, the zone of calcified matrix connects the epiphyseal plate to the diaphysis. A bone grows in length when osseous tissue is added to the diaphysis. Bones continue to grow in length until early adulthood. The rate of growth is controlled by hormones, which will be discussed later.
When the chondrocytes in the epiphyseal plate cease their proliferation and bone replaces all the cartilage, longitudinal growth stops. All that remains of the epiphyseal plate is the ossified epiphyseal line Figure 6. While bones are increasing in length, they are also increasing in diameter; growth in diameter can continue even after longitudinal growth ceases.
This growth by adding to the free surface of bone is called appositional growth. Appositional growth can occur at the endosteum or peristeum where osteoclasts resorb old bone that lines the medullary cavity, while osteoblasts produce new bone tissue.
The erosion of old bone along the medullary cavity and the deposition of new bone beneath the periosteum not only increase the diameter of the diaphysis but also increase the diameter of the medullary cavity. However, in adult life, bone undergoes constant remodeling, in which resorption of old or damaged bone takes place on the same surface where osteoblasts lay new bone to replace that which is resorbed.
Injury, exercise, and other activities lead to remodeling. Those influences are discussed later in the chapter, but even without injury or exercise, about 5 to 10 percent of the skeleton is remodeled annually just by destroying old bone and renewing it with fresh bone.
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