Osteogenesis: The Formation Of Bones

Osteogenesis is the process of bone formation. It occurs both during embryonic development, as in the repair of fractures or during growth.

Osteogenesis is the biological process by which bones are formed. It begins during the eighth week of embryonic development, and is also the process on which the repair of fractures depends.

Formation and development of the skeleton

All the bones of the human skeleton are derived from three embryonic structures:  the somites, the mesoderm, and the neural crest.

The osteogenesis process consists of the transformation of pre-existing tissue into bone tissue. There are two mechanisms:

• Intramembranous ossification. This is the name given to the direct transformation of the original tissue into bone tissue.

• Endochondral ossification. This process is somewhat more complex and takes place in two stages. First, the initial tissue is replaced by cartilage, then the cartilage ossifies.

Embryonic structures that give rise to bones

Somites are transient embryonic structures and are essential for the development of the pattern of segmented structures typical of vertebrates.

From the somites derive the bones that are part of the central axis of the body or axial skeleton. These are the bones of the skull and hearing, the hyoid, the ribs, the sternum and the spine.

The mesoderm is the middle layer (one of the three cell layers) from which the entire embryo develops.

Initially, there are three layers of cells: an outer, an intermediate, and an inner. Thanks to a complex process of differentiation, each and every one of these is developed from them.

 Finally , the neural crest is a transitory cell formation, typical of the first stages of development.

It has a fundamental characteristic: the pluripotentiality of its cells. That is, cells can give rise to almost any type of final structure of the body.

Regarding the skeleton , they give rise to the craniofacial bones, cartilage and other structures.

Intramembranous ossification process

Through this process, the flat bones of the skull are formed. As its name suggests, ossification occurs within a connective tissue membrane. Some of the cells in this membrane will become osteoblasts, the cells that make up the bone matrix. Others will do so in cells that are part of the small blood vessels that supply the bones.

The osteoblasts group together forming what is known as the ossification center , around which the bone will progressively form. These cells synthesize and release the necessary components to create a matrix capable of capturing calcium salts.

In this way, the initial membrane ossifies. The transformation of embryonic cells into osteoblasts occurs thanks to the activation of the transcription factor CBFA1. In turn, the activation of CBFA1 depends on the BMP proteins.

Endochondral ossification process

This other process is characterized by the formation of cartilage from the embryonic tissue and its subsequent ossification. For this, five stages are necessary:

• Cells express two transcription factors: Pax 1 and Scleraxis,  fundamental for the activation of the genes that will convert the original cells into cartilage. The expression of transcription factors is possible thanks to the fact that some cells induce their neighbors to do so in a paracrine manner.

• The cells that have expressed the necessary genes then clump together and become chondrocytes. 

• These chondrocytes multiply rapidly and form a kind of “blueprint” for future bone.

• In a fourth step, the multiplication stops and the chondrocytes increase in size.

• Finally, the cartilage mold is traversed by the forming blood vessels. The chondrocytes die progressively, being replaced by osteoblasts.

Osteoblasts and osteoclasts

Unlike osteoblasts, osteoclasts are cells responsible for bone destruction.

Osteogenesis imperfecta: crystal bone disease

Osteogenesis imperfecta is a genetic disease, characterized by excessive weakness of the bones. People who suffer from it suffer fractures almost constantly. Other associated problems are deafness, visual difficulties or constipation.

The disease is due to mutations that alter collagen I, an essential component in the bone matrix. The lack of this substance is responsible for the excessive fragility of the bones of those affected.

Osteopetrosis: too dense bones

Osteopetrosis is a rare congenital disease, characterized by a pathological increase in bone density. It is the consequence of an imbalance between the action of osteoblasts and osteoclasts.

In most cases, due to mutations, the carbonic anhydrase of the osteoclasts is altered, making them dysfunctional.

People with this disease also suffer fractures because the bones formed are abnormal.