Intramembranous ossification

Intramembranous ossification

Intramembranous ossification is one of the two processes during fetal development of the mammalian skeletal system in which bone tissue is created. It is also an essential process during the healing of bone fractures Brighton, Carl T. and Robert M. Hunt (1991), "Early histological and ultrastructural changes in medullary fracture callus", "Journal of Bone and Joint Surgery", 73-A (6): 832-847] and the rudimentary formation of bones of the head. Netter, Frank H. (1987), "Musculoskeletal system: anatomy, physiology, and metabolic disorders". Summit, New Jersey: Ciba-Geigy Corporation ISBN 0914168886, p.129] Unlike endochondral ossification, which is the other process, cartilage is not present during intramembranous ossification.

Creation of bone tissue

Mesenchymal stem cells, or MSCs, within human mesenchyme or the medullary cavity of a bone fracture initiate the process of intramembranous ossification. An MSC is an unspecialized cell whose morphology undergoes characteristic changes as it develops into an osteoblast. MSCs are long and thin, and their small cell body has a few cell processes that are also long and thin. The cell body contains a large, round nucleus with a prominent nucleolus which is surrounded by finely dispersed chromatin particles, giving the nucleus a clear appearance. The remainder of the cell body contains a small amount of Golgi apparatus, rough endoplasmic reticulum, mitochondria, and polyribosomes. The cells are widely dispersed and the adjacent extracellular matrix is populated by a few reticular fibrils but is devoid of the other types of collagen fibrils. This morphology is characteristic of a mesenchymal stem cell.Brighton and Hunt (1991)]

Some of the MSCs begin to replicate until they have formed a small, dense aggregation of cells, a nodule. At this point the MSCs stop replicating and changes in their morphology begin to occur. The cell body becomes larger and rounder, and the long, thin cell processes are no longer present. The amount of Golgi apparatus and rough endoplasmic reticulum increases. Eventually, the cells within the aggregate acquire the morphologic characteristics of an osteoprogenitor cell.Brighton and Hunt (1991)]

Changes in the morphology of the osteoprogenitor cells begin to occur. Their shape becomes more columnar and the amount of Golgi apparatus and rough endoplasmic reticulum increases. 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 create osteoid at its center.Brighton and Hunt (1991)]

As the amount of osteoid increases some of the osteoblasts become incorpoated within it to become osteocytes. Eventually, the osteoid mineralizes. This small structure, which began as a diffuse collection of MSCs, contains osteoid which has become mineralized, is lined externally by active osteoblasts, and contains osteocytes. This small structure has become rudimentary bone tissue and this is a brief description of how it was created.Brighton and Hunt (1991)]


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.


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

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