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 neural cest; the limb skeleton forms from lateral plate mesoderm; and the axial skeleton forms from paraxial mesoderm (sclerotome). There are two methods of osteogenesis. Both involve the transformation of pre - existing mesenchymal tissue into bone.

1. Intramembranous Ossification - direct conversion of mesenchymal tissue into bone. Occurs in production of the skull.
2. Endochondrial Ossification - mesechymal tissue first differentiates into cartilage, then into bone. This occurs in the production of 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.

1. Proliferating limb mesenchyme condenses.
2. The increased cell density triggers mesenchymal cells to differentiate into chondrocytes. Proliferation continues.
3. The bone shape is formed, with a diaphysis (shaft) and epiphysis (bulbous ends).
4. 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 epiphysis are pushed away from each other.
5. After 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.
6. 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.
7. There is no perichondrium surrounding the eiphysis.
   • This allows for expansion in length of the bone, but means that there are no surrounding oasteoblasts 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.
8. The bone becomes covered in a layer containing osteoblasts.

• Cartilage is not replaced by bone in two areas:

In between the diaphysis and epiphysis, a region called the epiphyseal growth plate (EPG).

At the ends of the epiphysis, between the joints. Acts as a shock absorber.

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.
• The EPG is 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 - chondrosytes enlarge and then die.
5. Dead cells become the matrix for bone growth.

Girth

• The perisosteum lines the outer surfae 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 bone diameter.
  • When osteoclasts start removing less bone, or osteoblasts start adding more bone, the girth increases.