During embryonic development most bones form via mesenchymal condensations. In the case of the bones of the skull, these condensations then differentiate directly into bone cells in the process called intramembranous ossification. However, the long bone process is different and alows for growth until puberty.

Long bones grow on a template of cartilage, in a process called endochondral ossification. Initially, the mesenchymal condensations differentiate into cartilage, populated by cells called the chondrocytes. The template then condenses and becomes hypoxic in the middle. This further stimulates the differentiation of the cells and induces secretion of certain molecules which attract blood vessels, and with them, blood forming cells. The bone is then layed down on the template of cartilage. The remaining cartilage continues to expand and die, driving the long bone formation. Later on in development, another event of blood invasion occurs at the end of the bones and a secondary centre of ossification forms. The cartilage between the two centres of ossification continues to drive the long bone formation until puberty, when its activity seizes and the bone elements fuse together.

The diagram below illustrates this process using Alcian Blue (cartilage specific stain) and Alizarin Red (bone specific stain) of developing mouse specimens:

 

Interesting fact: Cartilage tissue is not mineralised and doesn’t show on an X-ray. See if you can spot the difference between the young and adult knee Xray below:

The structure responsible for the long bone growth is entirely made out of cartilage. it’s called the cartilage growth plate. The growth plate consists solely of one type of cell, called the chondrocyte, however, along the height of the growth plate, chondrocytes exist in different differentiation stages, as illustrated below.

Chondrocytes in the resting zone form a pool of cells for the rest of the structure. As they exit this zone, they flatten and stat dividing, thus driving the long bone growth. Upon division they are aligning into the columns along the axis of the growth plate. Towards the bottom of the structure, the chondrocytes enlarge (hypertrophy), start secreting a different cocktail of molecules, which attract the blood vessel invasion, and finally die, leaving behind a scaffold of proteins onto which the new bone is deposited.

As you can appreciate from the story above, endochondral ossification is a tightly regulated and complex process. Due to various mutations many things can go wrong, resulting in a group of genetic conditions collectively known as skeletal dysplasias.