Endochondral Ossification

Endochondral ossification is an INDIRECT form of ossification. It originates with mesenchymal tissue, which then transitions to a hyaline cartilaginous model, and then transitions to bone. Most bones develop through this process (think of the long bones (eg, the femur)). “endo” means “within” and “chondral” means “cartilage”. A mesenchymal cell model (template) forms in the shape of a long bone and is populated with mesoderm-derived mesenchymal cells. Mesenchymal cells transition into chondroblasts (cartilage-producing cells) and become chondrocytes (cartilaginous cells that reside within the cartilage matrix).

• The transcription factor: SOX9 is a key gene that promotes this differentiation from mesenchyme to chondroblast.

Chondrocytes are lipid-containing cartilaginous cells that possess the structural components of cartilage: collagen, proteoglycans, and glycosaminoglycans. They are usually found in clusters (isogenic groups) of recently divided cells. Perichondrium surrounds the cartilage (hence “peri” for “around” and “chondrium” for cartilage). The perichondrium is a dense but well-vascularized fibrous tissue both protects the underlying cartilage and supplies key cells for growth and development, namely chondroblasts and osteoblasts. At the bone shaft (the diaphysis), perichondrium becomes periosteum. Osteoblasts lay down peripheral bone (compact bone) that forms a “bone collar”. The bone collar is essential for the formation of the primary ossification center because it starves the cartilage of necessary nutrients (limits their diffusion). Chondrocytes hypertrophy at the bone ends (the epiphyses). They replicate and divide to produce bone growth in a linear direction, called interstitial growth, at the epiphyseal ends. Within the primary ossification center, in the center of the bone, the chondrocytes hypertrophy but, here, they lack the nutrients to support cell division. Hypertrophic chondrocytes in the ossification center secrete a matrix that becomes calcified (essentially a calcified core), which further starves the ossification center of nutrients and promotes further cartilage-cell death. Chondrocyte apoptosis releases factors like vascular endothelial cell growth factor (VEGF), which induces the sprouting of blood vessels (vascular invasion). Show that the calcified core now cavitates. The cavity in the center of bone is called the medullary cavity. The periosteal bud is a descriptive term (rather than a singular anatomical structure) for a collection of key materials for production of primary spongiosa (new spongy bone).

• Vasculature
• Osteogenic cells
• Osteoblasts (bone-producing)
• Osteoclasts (bone-resorbing)
• Hematopoietic stem cells.

The periosteal bud vasculature possesses key factors that allow it to pass through the hard compact bone and feed the ossification center, so that spongy bone forms. The osteoblasts form new bone (primary spongiosa). Vascular invasion at the epiphyses forms the secondary ossification centers. We can think of secondary ossification in the same way we do primary ossification except there is no bone collar. Thus, there is no outer layer starving the epiphysis of nutrients. Rather the rapid growth and cartilage-cell death leads to ossification at these centers. The only remaining growth cartilage is found at the epiphyseal plates, in between the diaphysis and the epiphyses. These epiphyseal plates (growth plates) persist until the completion of interstitial growth (we reach our final height), after which time they become the epiphyseal lines.