Endochondral ossification is one of the two essential processes during fetal development of the

mammal Mammals () are a group of vertebrate animals constituting the class Mammalia (), characterized by the presence of mammary glands which in females produce milk for feeding (nursing) their young, a neocortex (a region of the brain), fur ...

ian

skeletal system A skeleton is the structural frame that supports the body of an animal. There are several types of skeletons, including the exoskeleton, which is the stable outer shell of an organism, the endoskeleton, which forms the support structure inside ...

by which bone tissue is produced. Unlike intramembranous ossification, the other process by which bone tissue is produced,

cartilage Cartilage is a resilient and smooth type of connective tissue. In tetrapods, it covers and protects the ends of long bones at the joints as articular cartilage, and is a structural component of many body parts including the rib cage, the neck ...

is present during endochondral ossification. Endochondral ossification is also an essential process during the rudimentary formation of long bones, the growth of the

length Length is a measure of distance. In the International System of Quantities, length is a quantity with dimension distance. In most systems of measurement a base unit for length is chosen, from which all other units are derived. In the Inte ...

of long bones, and the natural healing of bone fractures.

Growth of the cartilage model

The cartilage model will grow in length by continuous cell division of

chondrocyte Chondrocytes (, from Greek χόνδρος, ''chondros'' = cartilage + κύτος, ''kytos'' = cell) are the only cells found in healthy cartilage. They produce and maintain the cartilaginous matrix, which consists mainly of collagen and prote ...

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

The first site of

ossification Ossification (also called osteogenesis or bone mineralization) in bone remodeling is the process of laying down new bone material by cells named osteoblasts. It is synonymous with bone tissue formation. There are two processes resulting in ...

occurs in the primary center of ossification, which is in the middle of diaphysis (shaft). Then: #Formation of periosteum #: The

perichondrium The perichondrium (from Greek el, περί, peri, around, label=none and el, χόνδρος, chondros, cartilage, label=none) is a layer of dense irregular connective tissue that surrounds the cartilage of developing bone. It consists of two s ...

becomes the periosteum. The periosteum contains a layer of undifferentiated cells (osteoprogenitor cells) which later become

osteoblast Osteoblasts (from the Greek language, Greek combining forms for "bone", ὀστέο-, ''osteo-'' and βλαστάνω, ''blastanō'' "germinate") are cell (biology), cells with a single Cell nucleus, nucleus that synthesize bone. However, in the p ...

s. #Formation of

bone collar The bone collar is a cuff of periosteal bone that forms around the diaphysis of the hyaline cartilage model in developing long bones.Wheater's Functional Histology, 5th ed. Young, Lowe, Stevens and Heath. The bone collar appears during endochondr ...

#: The osteoblasts secrete osteoid against the shaft of the cartilage model (Appositional Growth). This serves as support for the new bone. #Calcification of matrix #:

Chondrocyte Chondrocytes (, from Greek χόνδρος, ''chondros'' = cartilage + κύτος, ''kytos'' = cell) are the only cells found in healthy cartilage. They produce and maintain the cartilaginous matrix, which consists mainly of collagen and prote ...

s in the primary center of ossification begin to grow (hypertrophy). They stop secreting

collagen Collagen () is the main structural protein in the extracellular matrix found in the body's various connective tissues. As the main component of connective tissue, it is the most abundant protein in mammals, making up from 25% to 35% of the whol ...

and other proteoglycans and begin secreting

alkaline phosphatase The enzyme alkaline phosphatase (EC 3.1.3.1, alkaline phosphomonoesterase; phosphomonoesterase; glycerophosphatase; alkaline phosphohydrolase; alkaline phenyl phosphatase; orthophosphoric-monoester phosphohydrolase (alkaline optimum), systematic ...

, an enzyme essential for mineral deposition. Then calcification of the matrix occurs and osteoprogenitor cells that entered the cavity via the periosteal bud, use the calcified matrix as a scaffold and begin to secrete osteoid, which forms the bone trabecula. Osteoclasts, formed from

macrophage Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer ce ...

s, break down spongy bone to form the medullary (bone marrow) cavity.

Secondary center of ossification

About the time of birth in mammals, a secondary ossification center appears in each end (epiphysis) of long bones. Periosteal buds carry

mesenchyme Mesenchyme () is a type of loosely organized animal embryonic connective tissue of undifferentiated cells that give rise to most tissues, such as skin, blood or bone. The interactions between mesenchyme and epithelium help to form nearly every ...

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 20 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 diaphysis occurs by deposition of bone beneath the periosteum. Osteoclasts in the interior cavity continue to resorb 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

During endochondral ossification, five distinct zones can be seen at the light-microscope level.

Fracture healing

During

fracture Fracture is the separation of an object or material into two or more pieces under the action of stress. The fracture of a solid usually occurs due to the development of certain displacement discontinuity surfaces within the solid. If a displ ...

healing, cartilage is often formed and is called callus. This cartilage ultimately develops into new bone tissue through the process of endochondral ossification. Recently it has been shown that biomimetic bone like

apatite Apatite is a group of phosphate minerals, usually hydroxyapatite, fluorapatite and chlorapatite, with high concentrations of OH−, F− and Cl− ions, respectively, in the crystal. The formula of the admixture of the three most common ...

inhibits formation of bone through endochondral ossification pathway via hyperstimulation of extracellular calcium sensing receptor (CaSR).

Examples in human body

Tubular and flat bones, vertebrae, the skull base, ethmoids, and the ends of the clavicles are formed by endochondral ossification.

Additional images

File:Proximal tibia Masson Goldner Trikrom rabbit 600x growth zone.jpg, Masson Goldner trichrome stain of growth plate in a rabbit tibia. File:Gray79.png, Section of fetal bone of cat. ir. Irruption of the subperiosteal tissue. p. Fibrous layer of the periosteum. o. Layer of osteoblasts. im. Subperiosteal bony deposit. (From Quain’s “Anatomy,” E. A. Schäfer.)

References

{{Bone and cartilage Animal developmental biology Skeletal system