Bone & Joint Development Processes

Instructor: Cheryl Rosenfeld

Cheryl has taught veterinary and medical student for over 20 years and has a DVM and PhD degree in reproductive biology.

In this lesson, we consider how bones and joints develop. As part of this lesson, we will consider the two types of bone formation, intramembranous and endochondral osteogenesis, as well as how these two processes differ and compare to each other. Updated: 03/02/2021

Mesenchyme Differentiation Into Bone

Mesenchyme can differentiate into bone via two mechanisms.

  • Intramembranous osteogenesis
  • Endochondral osteogenesis

Intramembranous osteogenesis is evident in flat bones of the skull and the periosteal region. Mesenchymal cells will differentiate into osteoblasts. Osteoblasts proceed to produce a matrix, the osteoid, in these regions. It is considered a calcified matrix upon the addition of calcium salts. Some osteoblasts will become entrapped in this calcified matrix, whereupon they are considered osteocytes, or bone keeper cells. All nutrients have to penetrate the calcified matrix via diffusion, and thus, osteocytes have gap junctions between them that permit the exchange of nutrients and ions.

Endochondral (intra-cartilaginous) osteogenesis is one of the main forms of bone development in the long bones, the femur, tibia, radius, and ulna. Mesenchymal tissue in these regions first differentiates into hyaline cartilage. The hyaline cartilage model that can grow via appositional and interstitial growth results in an increased lengthening of the bones. As the cartilage cells proliferate, the cells continue to extend beyond the underlying vascular supply. This also results in calcification of the cartilage matrix, which acts as a further barrier to nutrients reaching the chondrocytes. These cells also undergo enlargement (hypertrophy). Correspondingly, blood vessels from the periosteum, termed periosteal bud, penetrate into the bone medulla. These blood vessels carry precursor mesenchymal cells that will differentiate into osteoblasts. Once at the site, osteoblasts will begin to produce osteoid, which then becomes calcified. The degenerating cartilage will eventually be enzymatically destroyed by osteoclasts.

Once the osteoblasts are in the area, the bone formation process is identical to intramembranous osteogenesis. The only difference between the two types of osteogenesis is that endochondral osteogenesis involves mesenchymal cells first differentiating into cartilage cells. The degenerating cartilage is eventually replaced by other mesenchymal cells that will differentiate into osteoblasts. The diaphyseal region of the bone is considered the primary center of ossification, whereas, the epiphyses are considered the secondary centers of ossification. The physis (growth plate) that is just underneath the epiphyses will remain as hyaline cartilage until puberty, whereupon it is fully converted to bone.

Joint Limb Formation

While the bones are forming, the joints, regions where one bone meets up with another bone, are also forming. As with the bones, mesenchyme is also important for joint formation. In the skull, mesenchyme will differentiate into fibrous connective tissue that bridges the spaces between developing bones. During embryonic development, the gaps between the bones that make up the skull are wide and termed fontanelles. After birth, the skull bones will expand to reduce the space between such bones to the point they are termed suture lines, where the bones are connected via a thin layer of fibrous connective tissue.

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