This animation starts with histogenesis of the hyaline cartilage (i.e. chondrogenesis) in a 4-week-old embryo. Mesenchymal cells, blood capillaries and the intercellular substance are shown. In addition, the animation shows the condensation of the mesenchymal cells and the formation of a chondrific center or scleroblastema, whose cells secrete the cartilage matrix, thus creating a piece of precartilage. This precartilage piece is described in detail. Two mechanisms of (pre)cartilage growth are shown: interstitial and appositional. The sequence ends with a 7-week-old embryo, illustrating the formation of the first piece of hyaline cartilage.

Then, magnification is reduced to show further growth of the hyaline cartilage.

The next sequences show the growth of the cartilage piece, or cartilage model. The last diagram of the sequence defines the diaphysis, epiphyses, cartilage canals, perichodrium and blood vessels.

Next, the periosteal bony band forms around the diaphysis, and its function is animated. The consequences of the formation of the periosteal bony band are shown in approximately 10- and 11-week-old fetuses (including the arrest of mitoses within the diaphysis, hypertrophy and necrosis of chondrocytes, calcification of the cartilage matrix and the formation of the calcification point). The penetration of a periosteal bud, composed of a capillary loop, young mesenchymal cells and chodrolytic cells, into the necrotic diaphysis is shown in an approximately 12-week-old fetus. The formation of the diaphyseal or primary ossification center along with the growth and evolution of the periosteal bud are animated through the 12th week.

To describe more precisely events within the diaphysis after the formation of the periosteal bony band, the next sequence magnifies the diaphysis of the cartilage model, beginning with an approximately 11-week-old fetus and detailing the structure of the diaphysis.

Besides the periosteal bony band and its osteocytes, the diagram also shows the periosteum with its cambium (i.e. osteogenic layer) rich in young mesenchymal cells. Within the diaphysis are the non-calcified and calcified cartilage matrix as well as normal and hypertrophied chondrocytes situated in their lacunae. A capillary loop, located outside the diaphysis, is ready to penetrate the diaphysis. This occurs in the next sequence: a multinuclear structure on the tip of the capillary loop begins to perforate the periosteal bony band with the locally formed osteoclasts. Young mesenchymal cells are located within the perforation stream. These three components compose the periosteal bud. The hypertrophied chondrocytes then disintegrate. In an approximately 12-week-old fetus, the periosteal bud enters the diaphysis, where osteoclasts form a cavity in which other elements of the periosteal bud spread (i.e. capillary loop and young mesenchymal cells).

A particularly long sequence animates the enlargement of the diaphyseal cavity, now called the primitive medullary cavity, in which young mesencyhmal cells form hematopoietic stem cells and a number of osteoblasts. The latter remain on the remnants of the eroded calcified cartilage matrix and start to produce the osteoid. In the meantime, the osteoclast enlarge the primitive medullary cavity. All of these elements compose the primary ossification center.

Because several events occur simultaneously during endochondral ossification, the next osteogenic events are given step-by-step. Therefore, the events within the primitive medullary cavity are temporarily set aside.

The first step shows the extension and thickening of the periosteal bony band through appositional growth.

This step is followed by hypertrophy of chondrocytes, calcification of the cartilage matrix and necrosis of hypertrophied chondrocytes. The next step shows the osteoblastic synthesis of osteoid, osteoclastic erosion of partitions between the chodrocytic lacunae followed by the invasion of cells from the primitive medullary cavity. Then, the osteoid is impregnated by calcium salts, and the immature bone forms. Because this bone develops within the cartilage model, it is also called endochondral or cartilage bone.

Since the primitive medullary cavity constantly enlarges, the next sequences show further thickening of the periosteal bony band followed by the erosion of its inner surface. In addition, the osteoclasts erode the non-calcified partitions, separating the empty lacunae of necrotic chodrocytes and thus contributing to the vertical extension of the primitive medullary cavity. With the enlargement of the latter, the capillary loop begins to sprout, so that its capillary loops follow the osteoclastic erosion. The hematopoietic stem cells near the blood sinuses of the primitive bone marrow are also animated.

In order to show the reaction of the epiphyses, i.e. the elongation of the cartilage model, magnification is reduced for all of these events. Two successive detailed diagrams with more than 20 legends show all zones between one of the epiphyses and the diaphysis as well as a cartilage canal with its capillary loop for an approximately 4-month-old fetus. The top of the epiphyseal cartilage is marked with an arrow to serve as a control for the elongation of the cartilage model.

For a fetus in the 5th month, the next sequence shows the chodroclastic erosion of partitions between the lacunae, the further advancement of capillary loops toward the epiphysis, the mitotic activity of chodrocytes, and the formation of cartilage cell columns. In this way, the cartilage model elongates.

In an approximately 8-mont-old fetus, a group of hypertrophic and necrotic chondrocytes develops within the epiphysis. In two sequences at the beginning of the 9th month, the cartilage matrix between the necrotic and hypetrophied chodrocytes becomes calcified and forms the epiphyseal calcification center. Then, the capillary loop with osteoclasts and young mesenchymal cells from the cartilage canal penetrate the calcification center and erode the epiphyseal or secondary ossification center. The next sequence, ending with a newborn, shows the osteoblasts covering the epiphyseal ossification center with the immature bone.

The diagram indicates the position of the articular cartilage and the epiphyseal plate. Further elongation of the cartilage model at the beginning of postnatal life is animated.

The next two sequences show the simultaneous erosion of the epiphyseal plate from the epiphysis and the diaphysis to explain the elongation of long bone in length, i.e. the growth of the whole body. The diagram corresponding to early postnatal life details the diaphysis, epiphysis, epiphyseal plate, epiphyseal ossification center, future articular cartilage as well as various zones visible within the epiphyseal plate. The erosion from the diaphyseal side and the proliferation of the chondrocytes within the epiphyseal plate are animated. The last sequence ends with the disappearance of the epiphyseal plate at the end of puberty, showing the formation of the definitive medullary cavity and the bone trabeculae of the cancellous bone.

The summary shows the principle of the endochodral ossification viewed under low magnification in a series of simplified diagrams.

As malformations of the endochondral ossification are shown, growths of long bones in cases of achondroplasia and gigantisam are compared with normal growth. The last diagram depicts patients with achondroplasia and gigantism as well a case of the fetal achodroplasia.

(This animation is essential for students of medicine, stomatology and biology as well as for departments of anatomy, histology, embryology and cell biology; it is also recommended for departments and clinics of pathology, pediatrics, orthopedics and orthopedic surgery.)