Intramembranous ossification is one of the two essential processes duringfetal development of thegnathostome (excludingchondrichthyans such assharks)skeletal system by which rudimentarybone tissue is created.Intramembranous ossification is also an essential process during the natural healing ofbone fractures[1] and the rudimentary formation ofbones of thehead.[2]
Unlikeendochondral ossification, which is the other process by which bone tissue is created during fetal development,cartilage is not present during intramembranous ossification.
Mesenchymal stem cells withinmesenchyme or themedullary cavity of a bone fracture initiate the process of intramembranous ossification. A mesenchymal stem cell, or MSC, is an unspecialized cell that can develop into anosteoblast. Before it begins to develop, themorphological characteristics of a MSC are: A smallcell body with a few cell processes that are long and thin; a large, roundnucleus with a prominentnucleolus that is surrounded by finely dispersedchromatin particles, giving the nucleus a clear appearance; and a small amount ofGolgi apparatus,rough endoplasmic reticulum,mitochondria, andpolyribosomes. Furthermore, the mesenchymal stem cells are widely dispersed within anextracellular matrix that is devoid of every type ofcollagen, except for a fewreticular fibrils.[1]
The process of intramembranous ossification starts when a small group of adjacent MSCs begin toreplicate and form a small, dense cluster of cells that is called anidus.[a] Once a nidus has been formed the MSCs within it stop replicating.At this point, morphological changes in the MSCs begin to occur: The cell body is now 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 nidus develop into, and display the morphologic characteristics of, anosteoprogenitor cell.[1]
At this stage of development, changes in the morphology of the osteoprogenitor cells occur: Their shape becomes more columnar and the amount of Golgi apparatus and rough endoplasmic reticulum increases. Eventually, all of the cells within the nidus develop into, and display the morphologic characteristics of, anosteoblast.Then the osteoblasts create an extracellular matrix containingType-I collagen fibrils, which isosteoid. The osteoblasts, while lining the periphery of the nidus, continue to form osteoid in the center of the nidus. Some of the osteoblasts become incorporated within the osteoid to becomeosteocytes.[1]
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 developed into woven bone, the most rudimentarybone tissue.[1]
The first step in the process is the formation of bonespicules which eventually fuse with each other and becometrabeculae. Theperiosteum 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 calledwoven bone. Eventually, woven bone is replaced bylamellar bone.
Embryologicmesenchymal cells (MSC) condense into layers of vascularized primitiveconnective tissue. Certain mesenchymal cells group together, usually near or around blood vessels, and differentiate into osteogenic cells which deposit bonematrixconstitutively. These aggregates of bonymatrix are called bone spicules. Separate mesenchymal cells differentiate intoosteoblasts, which line up along the surface of the spicule and secrete moreosteoid, which increases the size of the spicule.
As the spicules continue to grow, they fuse with adjacent spicules and this results in the formation oftrabeculae. Whenosteoblasts become trapped in the matrix they secrete, they differentiate intoosteocytes. Osteoblasts continue to line up on the surface which increases the size. As growth continues, trabeculae become interconnected andtrabecular bone is formed. The termprimary spongiosa is also used to refer to the initial trabecular network.
Theperiosteum is formed around the trabeculae by differentiating mesenchymal cells. The primary center of ossification is the area where bone growth occurs between theperiosteum and the bone. Osteogenic cells that originate from the periosteum increase appositional growth and abone collar is formed. The bone collar is eventually mineralized andlamellar bone is formed.
Osteons are components or principal structures of compact bone. During the formation of bone spicules,cytoplasmic processes from osteoblasts interconnect. This becomes thecanaliculi of osteons. Since bone spicules tend to form aroundblood 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.
The following bones develop in humans viaIntramembranous ossification:[3]
Other bone that formed by intramembranous ossification are: cortices of tubular and flat bones as well as thecalvaria, upper facial bones, tympanic temporal bone, vomer, and medial pterygoid process.[4]