Endochondral ossification

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Histological appearance of bone tissue formation.

Endochondral ossification is one of the two ways by which bone is formed. The process of bone formation and development begins as an embryo and continues until early adulthood. 

Endochondral ossification occurs in the long bones around the 6th embryonic week. It involves the formation of hyaline cartilage precursors from aggregated mesenchymal cells, and their subsequent systematic replacement by bone to form the growing skeleton.

The process of endochondral ossification can be divided into five stages:

• Formation of cartilage model: Mesenchymal cells begin their differentiation into chondroblasts giving rise to hyaline cartilage models. Chondroblasts continue to proliferate rapidly, organizing themselves into columns perpendicular to the long axis of growth. They eventually mature into chondrocytes.
• Cartilage calcification: Chondrocytes near the center of the cartilage model undergo hypertrophy and alter the contents of the extracellular matrix they secrete by adding collagen X and more fibronectin, a glycoprotein. This enables calcification of the tissue.
• Formation of primary ossification center: The cartilage model slowly becomes vascularized through penetration of vascular buds. Chondrocytes then undergo apoptosis due to decreased nutrient availability. Bone marrow is simultaneously formed by resorption of central portion of the cartilage precursor. Osteoprogenitor cells reach the cartilage model through the vascular buds and differentiate into osteoblasts. This process results in the formation of the primary ossification centers in the diaphysis (central part of bone).
• Formation of secondary ossification centers: While bone is slowly replacing cartilage in the diaphysis through proliferation of osteoblasts, cartilage continues to grow at the ends of the bone (epiphysis), thus increasing bone length. This is where the secondary ossification centers are formed.
• Epiphyseal plate formation: These rounded areas at either end of the bone are also known as the epiphyseal plates/growth plates, which boost longitudinal growth of bones after birth and into early adulthood.