Endochondral ossification is one of the two essential processes during fetal development of the mammalian 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. Endochondral ossification 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.
The cartilage model will grow in length by continuous cell division of chondrocytes, 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.
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The first site of ossification occurs in the primary center of ossification, which is in the middle of diaphysis (shaft). Then:
About the time of birth in mammals, 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 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.
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.
During endochondral ossification, five distinct zones can be seen at the light-microscope level.
|Zone of resting cartilage||This zone contains normal, resting hyaline cartilage.|
|Zone of proliferation / cell columns||In this zone, chondrocytes undergo rapid mitosis, forming distinctive looking stacks.|
|Zone of maturation / hypertrophy||In this zone, the chondrocytes undergo hypertrophy (become enlarged). Chondrocytes contain large amounts of glycogen and begin to secrete alkaline phosphatase.|
|Zone of calcification||In this zone, chondrocytes 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.|
During fracture 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 inhibits formation of bone through endochondral ossification pathway via hyperstimulation of extracellular calcium sensing receptor (CaSR).