Endochondral ossification
Encyclopedia
Endochondral ossification is one of the two essential processes during fetal development of the mammal
ian skeletal system
by which bone tissue is created. Unlike intramembranous ossification
, which is the other process by which bone tissue is created, cartilage
is present during endochondral ossification. It is also an essential process during the rudimentary formation of long bones, the growth of the length
of long bones, and the natural healing of bone fractures
.
s, which is accompanied by further secretion of extracellular matrix. This is called interstitial growth.
The process of appositional growth occurs when the cartilage model also grows in thickness due to the addition of more extracellular matrix on the peripheral cartilage surface, which is accompanied by new chondroblasts that develop from the perichondrium.
The first site of ossification occurs in the primary center of ossification, which is in the middle of diaphysis
(shaft). Then:
occurs by deposition of bone beneath the periosteum
. Osteoclast
s in the interior cavity continue to degrade bone until its ultimate thickness is achieved, at which point the rate of formation on the outside and degradation from the inside is constant.
During endochondral ossification, five distinct zones can be seen at the light-microscope level.
healing, cartilage is often formed and is called callus
. This cartilage ultimately develops into new bone tissue through the process of endochondral ossification.
Mammal
Mammals are members of a class of air-breathing vertebrate animals characterised by the possession of endothermy, hair, three middle ear bones, and mammary glands functional in mothers with young...
ian skeletal system
Skeleton
The skeleton is the body part that forms the supporting structure of an organism. There are two different skeletal types: the exoskeleton, which is the stable outer shell of an organism, and the endoskeleton, which forms the support structure inside the body.In a figurative sense, skeleton can...
by which bone tissue is created. Unlike intramembranous ossification
Intramembranous ossification
Intramembranous ossification is one of the two essential processes during fetal development of the mammalian skeletal system by which bone tissue is created. Unlike endochondral ossification, which is the other process by which bone tissue is created, cartilage is not present during intramembranous...
, which is the other process by which bone tissue is created, cartilage
Hyaline cartilage
Hyaline cartilage consists of a slimy mass, pearly bluish in colour with firm consistency and considerable collagen. It contains no nerves or blood vessels, and its structure is relatively simple....
is present during endochondral ossification. It is also an essential process during the rudimentary formation of long bones, the growth of the length
Epiphyseal plate
The epiphyseal plate is a hyaline cartilage plate in the metaphysis at each end of a long bone...
of long bones, and the natural healing of bone fractures
Bone healing
Bone healing, or fracture healing, is a proliferative physiological process in which the body facilitates the repair of a bone fracture....
.
Growth of the cartilage model
The cartilage model will grow in length by continuous cell division of chondrocyteChondrocyte
Chondrocytes are the only cells found in cartilage. They produce and maintain the cartilaginous matrix, which consists mainly of collagen and proteoglycans...
s, which is accompanied by further secretion of extracellular matrix. This is called interstitial growth.
The process of appositional growth occurs when the cartilage model also grows in thickness due to the addition of more extracellular matrix on the peripheral cartilage surface, which is accompanied by new chondroblasts that develop from the perichondrium.
Primary center of ossification
Diaphysis
The diaphysis is the main or mid section of a long bone. It is made up of cortical bone and usually contains bone marrow and adipose tissue ....
(shaft). Then:
- Formation of periosteum: The perichondriumPerichondriumThe perichondrium is a layer of dense irregular connective tissue which surrounds the cartilage of developing bone. It consists of two separate layers: an outer fibrous layer and inner chondrogenic layer. The fibrous layer contains fibroblasts, which produce collagenous fibers. The chondrogenic...
becomes the periosteumPeriosteumPeriosteum is a membrane that lines the outer surface of all bones, except at the joints of long bones. Endosteum lines the inner surface of all bones....
. The periosteum contains a layer of undifferentiated cells (osteoprogenitor cells) which later become osteoblastOsteoblastOsteoblasts are mononucleate cells that are responsible for bone formation; in essence, osteoblasts are specialized fibroblasts that in addition to fibroblastic products, express bone sialoprotein and osteocalcin.Osteoblasts produce a matrix of osteoid, which is composed mainly of Type I collagen...
s. - Formation of bone collarBone collarThe bone collar is a cuff of periosteal bone that forms around the diaphysis of the hyaline cartilage model in developing long bones....
: The osteoblasts secrete osteoidOsteoidIn histology, osteoid is the unmineralized, organic portion of the bone matrix that forms prior to the maturation of bone tissue. Osteoblasts begin the process of forming bone tissue by secreting the osteoid as several specific proteins...
against the shaft of the cartilage model (Appositional Growth). This serves as support for the new bone. - Calcification of matrix: ChondrocyteChondrocyteChondrocytes are the only cells found in cartilage. They produce and maintain the cartilaginous matrix, which consists mainly of collagen and proteoglycans...
s in the primary center of ossification begin to grow (hypertrophy). They stop secreting collagenCollagenCollagen is a group of naturally occurring proteins found in animals, especially in the flesh and connective tissues of mammals. It is the main component of connective tissue, and is the most abundant protein in mammals, making up about 25% to 35% of the whole-body protein content...
and other proteoglycanProteoglycanProteoglycans are proteins that are heavily glycosylated. The basic proteoglycan unit consists of a "core protein" with one or more covalently attached glycosaminoglycan chain. The point of attachment is a Ser residue to which the glycosaminoglycan is joined through a tetrasaccharide bridge...
s and begin secreting alkaline phosphataseAlkaline phosphataseAlkaline phosphatase is a hydrolase enzyme responsible for removing phosphate groups from many types of molecules, including nucleotides, proteins, and alkaloids. The process of removing the phosphate group is called dephosphorylation...
, an enzyme essential for mineral deposition. Then calcification of the matrix occurs and apoptosisApoptosisApoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...
of the hypertrophic chondrocytes occurs. This creates cavities within the bone. The exact mechanism of chondrocyte hypertrophy and apoptosis is currently unknown. - Invasion of periosteal bud: The hypertrophic chondrocytes (before apoptosis) secrete Vascular Endothelial Cell Growth Factor that induces the sprouting of blood vessels from the perichondrium. Blood vessels forming the periosteal bud invade the cavity left by the chondrocytes and branch in opposite directions along the length of the shaft. The blood vessels carry hemopoietic cells, osteoprogenitor cells and other cells inside the cavity. The hemopoietic cells will later form the bone marrowBone marrowBone marrow is the flexible tissue found in the interior of bones. In humans, bone marrow in large bones produces new blood cells. On average, bone marrow constitutes 4% of the total body mass of humans; in adults weighing 65 kg , bone marrow accounts for approximately 2.6 kg...
. - Formation of trabeculae: OsteoblastOsteoblastOsteoblasts are mononucleate cells that are responsible for bone formation; in essence, osteoblasts are specialized fibroblasts that in addition to fibroblastic products, express bone sialoprotein and osteocalcin.Osteoblasts produce a matrix of osteoid, which is composed mainly of Type I collagen...
s, differentiated from the osteoprogenitor cells that entered the cavity via the periosteal bud, use the calcified matrix as a scaffold and begin to secrete osteoidOsteoidIn histology, osteoid is the unmineralized, organic portion of the bone matrix that forms prior to the maturation of bone tissue. Osteoblasts begin the process of forming bone tissue by secreting the osteoid as several specific proteins...
, which forms the bone trabeculaTrabeculaA trabecula is a small, often microscopic, tissue element in the form of a small beam, strut or rod, generally having a mechanical function, and usually composed of dense collagenous tissue They can be composed of other materials; in the heart, for example, muscles such as trabeculae carneae...
. OsteoclastOsteoclastAn osteoclast is a type of bone cell that removes bone tissue by removing its mineralized matrix and breaking up the organic bone . This process is known as bone resorption. Osteoclasts were discovered by Kolliker in 1873...
s, formed from macrophageMacrophageMacrophages are cells produced by the differentiation of monocytes in tissues. Human macrophages are about in diameter. Monocytes and macrophages are phagocytes. Macrophages function in both non-specific defense as well as help initiate specific defense mechanisms of vertebrate animals...
s, break down spongy bone to form the medullary (bone marrow) cavity.
Secondary center of ossification
About the time of birth, a secondary ossification center appears in each end (epiphysis) of long bones. Periosteal buds carry mesenchyme and blood vessels in and the process is similar to that occurring in a primary ossification center. The cartilage between the primary and secondary ossification centers is called the epiphyseal plate, and it continues to form new cartilage, which is replaced by bone, a process that results in an increase in length of the bone. Growth continues until the individual is about 26 years old or until the cartilage in the plate is replaced by bone. The point of union of the primary and secondary ossification centers is called the epiphyseal line.Appositional bone growth
The growth in diameter of bones around the diaphysisDiaphysis
The diaphysis is the main or mid section of a long bone. It is made up of cortical bone and usually contains bone marrow and adipose tissue ....
occurs by deposition of bone beneath the periosteum
Periosteum
Periosteum is a membrane that lines the outer surface of all bones, except at the joints of long bones. Endosteum lines the inner surface of all bones....
. Osteoclast
Osteoclast
An osteoclast is a type of bone cell that removes bone tissue by removing its mineralized matrix and breaking up the organic bone . This process is known as bone resorption. Osteoclasts were discovered by Kolliker in 1873...
s in the interior cavity continue to degrade bone until its ultimate thickness is achieved, at which point the rate of formation on the outside and degradation from the inside is constant.
Histology
- Zone of resting cartilage. This zone contains normal, resting hyaline cartilageHyaline cartilageHyaline cartilage consists of a slimy mass, pearly bluish in colour with firm consistency and considerable collagen. It contains no nerves or blood vessels, and its structure is relatively simple....
. - Zone of proliferation. In this zone, chondrocyteChondrocyteChondrocytes are the only cells found in cartilage. They produce and maintain the cartilaginous matrix, which consists mainly of collagen and proteoglycans...
s undergo rapid mitosisMitosisMitosis is the process by which a eukaryotic cell separates the chromosomes in its cell nucleus into two identical sets, in two separate nuclei. It is generally followed immediately by cytokinesis, which divides the nuclei, cytoplasm, organelles and cell membrane into two cells containing roughly...
, forming distinctive looking stacks. - Zone of maturation / hypertrophy. It is during this zone that the chondrocytes undergo hypertrophy (become enlarged). Chondrocytes contain large amounts of glycogenGlycogenGlycogen is a molecule that serves as the secondary long-term energy storage in animal and fungal cells, with the primary energy stores being held in adipose tissue...
and begin to secrete alkaline phosphataseAlkaline phosphataseAlkaline phosphatase is a hydrolase enzyme responsible for removing phosphate groups from many types of molecules, including nucleotides, proteins, and alkaloids. The process of removing the phosphate group is called dephosphorylation...
. - Zone of calcification. In this zone, chondrocyteChondrocyteChondrocytes are the only cells found in cartilage. They produce and maintain the cartilaginous matrix, which consists mainly of collagen and proteoglycans...
s are either dying or dead, leaving cavities that will later become invaded by bone-forming cells. Chondrocytes here die when they can no longer receive nutrients or eliminate wastes via diffusion. This is because the calcified matrix is much less hydrated than hyaline cartilage. - Zone of ossification. Osteoprogenitor cells invade the area and differentiate into osteoblasts, which elaborate matrix that becomes calcified on the surface of calcified cartilage. This is followed by resorption of the calcified cartilage/calcified bone complex.
Fracture healing
During fractureBone fracture
A bone fracture is a medical condition in which there is a break in the continuity of the bone...
healing, cartilage is often formed and is called callus
Fibrocartilage callus
A fibrocartilage callus is a temporary formation of fibroblasts and chondroblasts which forms at the area of a bone fracture as the bone attempts to heal itself...
. This cartilage ultimately develops into new bone tissue through the process of endochondral ossification.