Bone & Cartilage Development - Anatomy & Physiology

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Introduction

Osteogenesis is the formation of bone. Bone forms from one of three lineages; the skull forms from the neural crest; the limb skeleton forms from the lateral plate mesoderm; and the axial skeleton forms from the paraxial mesoderm (sclerotome). There are two methods of osteogenesis. Both involve the transformation of the pre - existing mesenchymal tissue into bone.

1. Intramembranous Ossification - the direct conversion of mesenchymal tissue into bone. Occurs in production of the skull.

2. Endochondrial Ossification - the mesechymal tissue first differentiates into cartilage, then into bone. This occurs in the production of the limb and axial skeleton. Limb cartilage is produced in a proximal to distal direction as a continuous structure. It becomes punctuated with joints later, and then converted to bone.

Endochondrial Ossification

Bone formation via cartilage occurs in the following stages:

1. The proliferating limb mesenchyme condenses.

2. The increased cell density triggers mesenchymal cells to differentiate into chondrocytes. Proliferation continues and the bone shape is formed, with a diaphysis (shaft) and epiphysis (bulbous ends).

3. Chondrocytes in the middle of the diaphysis stop proliferating and undergo hypertrophy. The shaft is surrounded by the perichondrium, a restrictive membrane. This means that the bone can only grow in length, not width. The epiphyses are pushed away from each other.

4. After the chondrocytes have undergone hypertrophy, they die.

5. Osteoblasts on the inner side of the perichondrium invade the cartilage matrix. They then secrete the extra - cellular matrix, characteristic of bone.

6. Ossification occurs from the outside in. This is called primary ossification, or perichondrial ossification. Blood vessels invade the central region of the diaphysis to transport bone marrow stem cells and osteoclasts. The osteoclasts break down the cartilage matrix to allow room for the bone marrow.

There is no perichondrium surrounding the epiphysis, this allows for expansion in length of the bone, but means that there are no surrounding osteoblasts to invade. To achieve osteogenesis, blood vessels invade from the diaphysis and carry osteoblasts with them. In the epiphysis, osteoblasts initiate bone growth from the inside out. This is called secondary ossification. In some mammals, secondary ossification occurs after birth. The bone becomes covered in a layer containing osteoblasts.

Cartilage is not replaced by bone in two areas:

1. In between the diaphysis and epiphysis, a region called the epiphyseal growth plate (EPG).
2. At the ends of the epiphysis, between the joints. Acts as a shock absorber.

Development of Bone and Cartilage

Osteogenesis is the formation of bone. Bone forms from one of three lineages; the skull forms from the neural crest; the limb skeleton forms from the lateral plate mesoderm; and the axial skeleton forms from the paraxial mesoderm (sclerotome). There are two methods of osteogenesis;

1. Intramembranous Ossification

Forms the flat bones of skull and mandible. There is no cartilaginous precursor, the mesenchyme forms bone directly. The mesenchyme condenses, differentiates to pre-osteoblasts, then to osteoblasts. The osteoblasts synthesize osteoid (collagen and proteoglycans) causing mineralization and bone spicule formation. Spicules produce spongy bone. The bone growth can be described as appositional growth, where bone is laid down on the exterior (vs interior) surface of the developing bone. During bone development there is an increasing association with blood vessels and bone marrow is formed by the mesenchyme, between the bone and the blood vessels.

2. Endochondral Ossification

This is responsible for embryonic bone formation, as well as the growth in length. This occurs via a cartilaginous precursor. The mesenchyme condenses to form the bone outline. The increased cell density triggers core cells to differentiate to chondrocytes and begin secreting the cartilage matrix. Proliferation continues and the bone shape is formed, with a diaphysis (shaft) and epiphysis (bulbous ends). Chondrocytes in the middle of the diaphysis stop proliferating and undergo hypertrophy. The shaft is surrounded by the perichondrium, a restrictive membrane. This means that the bone can only grow in length, not width. The epiphyses are pushed away from each other. After the chondrocytes have undergone hypertrophy, they die. Osteoblasts on the inner side of the perichondrium invade the cartilage matrix. They then secrete the extra - cellular matrix, characteristic of bone. Ossification occurs from the outside in. This is called primary ossification, or perichondrial ossification. Blood vessels invade the central region of the diaphysis to transport bone marrow stem cells and osteoclasts. The osteoclasts break down the cartilage matrix to allow room for the bone marrow.

There is no perichondrium surrounding the epiphysis, this allows for expansion in length of the bone, but means that there are no surrounding osteoblasts to invade. To achieve osteogenesis, blood vessels invade from the diaphysis and carry osteoblasts with them. In the epiphysis, osteoblasts initiate bone growth from the inside out. This is called secondary ossification. In some mammals, secondary ossification occurs after birth. The bone becomes covered in a layer containing osteoblasts.

Cartilage is not replaced by bone in two areas: 1. In between the diaphysis and epiphysis, a region called the epiphyseal growth plate (EPG). 2. At the ends of the epiphysis, between the joints. Acts as a shock absorber.

For more information on bone and joint development, click here.

Bone Growth

Length

The epiphyseal growth plate (EPG) allows the bone to continue to grow in length after birth. The EPG is a region of continuous chondroblast differentiation and maturation and can be divided into five zones:

1. Germinal Zone - chondroblast division at a low rate, and self renewal.
2. Proliferation Zone - chondroblast division at a fast rate.
3. Maturation Zone - chondroblast differentiation into chondrocytes.
4. Hypertrophic Zone - chondrocytes enlarge and then die.
5. Dead cells become the matrix for bone growth.

Girth

The periosteum lines the outer surface of the diaphysis of the bone. It has a cellular inner layer, consisting of osteoblasts, and a fibrous outer layer. The endosteum lines the inner surface of the diaphysis of the bone. It contains osteoblasts and osteoclasts. Bone growth occurs by a shift in the equilibrium between osteoblasts and osteoclasts. Osteoblasts on the outside in the periosteum add bone to increase the bone's diameter. Osteoclasts on the inside in the endosteum remove this bone to maintain the bone diameter. When osteoclasts start removing less bone, or osteoblasts start adding more bone, the girth increases.

Joint Formation

Joints begin to form as the mesenchyme is condensing. Joint-forming cells develop different characteristics to cartilage precursors; they are flat and densely packed. The region where these joint-forming cells exist is called the "interzone". There are three layers in the interzone, a middle layer of low density with regions of high density either side. The high density regions form cartilage. The middle layer is eliminated by cell death, forming the joint space.