Intramembranous ossification

Intramembranous ossification^[1] is one of the two essential processes during fetal development of the mammalian skeletal system resulting in the creation of bone tissue. Unlike endochondral ossification, which is the other process, cartilage is not present during intramembranous ossification. It is also an essential process during the natural healing of bone fractures^[2] and the rudimentary formation of bones of the head.^[3]

Creation of bone tissue

Mesenchymal stem cell

Mesenchymal stem cells, or MSCs, within human mesenchyme or the medullary cavity of a bone fracture initiate the process of intramembranous ossification. A MSC is an unspecialized cell whose morphology undergoes characteristic changes as it develops into an osteoblast. Before it begins to develop, the morphological characteristics of a MSC are: a small cell body with a few cell processes that are long and thin; a large, round nucleus with a prominent nucleolus that is surrounded by finely dispersed chromatin particles, giving the nucleus a clear appearance; a small amount of Golgi apparatus, rough endoplasmic reticulum, mitochondria, and polyribosomes; and the cells are widely dispersed within an extracellular matrix that is devoid of every type of collagen except for a few reticular fibrils.^[2]

Osteoprogenitor cells within a dense cell aggregate

Then a small group of adjacent MSCs begin to replicate until they have formed a small, dense aggregation of cells, a nodule. Once a nodule has been formed the MSCs within it stop replicating. At this point, changes in the morphology of the MSCs occur: the cell body becomes larger and rounder; the long, thin cell processes are no longer present; and the amount of Golgi apparatus and rough endoplasmic reticulum increases. Eventually, all of the cells within the aggregate display the morphologic characteristics of an osteoprogenitor cell.^[2]

Osteoblasts, several displaying a prominent Golgi Apparatus, creating osteoid in the center of the aggregate

At this stage of development, changes in the morphology of the osteoprogenitor cells occur: their shape becomes more columnar; the amount of Golgi apparatus and rough endoplasmic reticulum increases; and the cells begin to create an extracellular matrix consisting of Type-I collagen fibrils. This matrix is osteoid and the cells that created it are osteoblasts. The osteoblasts, while lining the periphery of the nodule, continue to form osteoid at its center and some of them become incorpoated within it to become osteocytes.^[2]

Osteoblasts creating rudimentary bone tissue

At this point, the osteoid becomes mineralized resulting in a nidus consisting of mineralized osteoid that contains osteocytes and is lined by active osteoblasts. The nidus, that began as a diffuse collection of MSCs, has become rudimentary bone tissue.^[2]

Overview

The first step in the process is the formation of bone spicules which eventually fuse with each other and become trabeculae. The periosteum is formed and bone growth continues at the surface of trabeculae. Much like spicules, the increasing growth of trabeculae result in interconnection and this network is called woven bone. Eventually, woven bone is replaced by lamellar bone.

Process Overview

• Mesenchyme cell in the membrane become osteochondral progenitor cell
• osteochondral progenitor cell specialized to become osteoblast
• Osteoblast produce bone matrix and surrounded collagen fiber and become osteocyte
• As the result process trabeculae will develop
• Osteoblast will trap trabeculae to produce bone
• Trabeculae will join together to produce spongy cell
• Cells in the spongy cell will specialize to produce red bone marrow
• Cells surrounding the developing bone will produce periosteum
• Osteoblasts from the Periosteum on the bone matrix will produce compact bone

Formation of bone spicules

Embryologic mesenchymal cells (MSC) condense into layers of vascularized primitive connective tissue. Certain mesenchymal cells group together, usually near or around blood vessels, and differentiate into osteogenic cells which deposit bone matrix constitutively. These aggregates of bony matrix are called bone spicules. Separate mesenchymal cells differentiate into osteoblasts, which line up along the surface of the spicule and secrete more osteoid, which increases the size of the spicule.

Formation of woven bone

As the spicules continue to grow, they fuse with adjacent spicules and this results in the formation of trabeculae. When osteoblasts become trapped in the matrix they secrete, they differentiate into osteocytes. Osteoblasts continue to line up on the surface which increases the size. As growth continues, trabeculae become interconnected and woven bone is formed. The term primary spongiosa is also used to refer to the initial trabecular network.

Primary center of ossification

The periosteum is formed around the trabeculae by differentiating mesenchymal cells. The primary center of ossification is the area where bone growth occurs between the periosteum and the bone. Osteogenic cells that originate from the periosteum increase appositional growth and a bone collar is formed. The bone collar is eventually mineralized and lamellar bone is formed.

Formation of osteon

Osteons are units or principal structures of compact bone. During the formation of bone spicules, cytoplasmic processes from osteoblasts interconnect. This becomes the canaliculi of osteons. Since bone spicules tend to form around blood vessels, the perivascular space is greatly reduced as the bone continues to grow. When replacement to compact bone occurs, this blood vessel becomes the central canal of the osteon.

See also

• Endochondral ossification
• Ossification

References

• Martin, RB; DB Burr; NA Sharkey (1998), Skeletal Tissue Mechanics, Chapter 2, Springer-Verlag