Intramembranous ossification is one of the two essential processes during fetal development of the gnathostome (excluding chondrichthyans such as

shark Sharks are a group of elasmobranch cartilaginous fish characterized by a ribless endoskeleton, dermal denticles, five to seven gill slits on each side, and pectoral fins that are not fused to the head. Modern sharks are classified within the ...

skeletal system A skeleton is the structural frame that supports the body of most animals. There are several types of skeletons, including the exoskeleton, which is a rigid outer shell that holds up an organism's shape; the endoskeleton, a rigid internal fra ...

by which rudimentary

bone tissue A bone is a Stiffness, rigid Organ (biology), organ that constitutes part of the skeleton in most vertebrate animals. Bones protect the various other organs of the body, produce red blood cell, red and white blood cells, store minerals, provi ...

is created. Intramembranous ossification is also an essential process during the natural healing of bone fractures and the rudimentary formation of

bone A bone is a rigid organ that constitutes part of the skeleton in most vertebrate animals. Bones protect the various other organs of the body, produce red and white blood cells, store minerals, provide structure and support for the body, ...

s of the

head A head is the part of an organism which usually includes the ears, brain, forehead, cheeks, chin, eyes, nose, and mouth, each of which aid in various sensory functions such as sight, hearing, smell, and taste. Some very simple ani ...

. Unlike

endochondral ossification Endochondral ossification is one of the two essential pathways by which bone tissue is produced during fetal development and bone healing, bone repair of the mammalian skeleton, skeletal system, the other pathway being intramembranous ossificatio ...

, which is the other process by which bone tissue is created during fetal development,

cartilage Cartilage is a resilient and smooth type of connective tissue. Semi-transparent and non-porous, it is usually covered by a tough and fibrous membrane called perichondrium. In tetrapods, it covers and protects the ends of long bones at the joints ...

is not present during intramembranous ossification.

Formation of woven bone

Mesenchymal stem cell Mesenchymal stem cells (MSCs), also known as mesenchymal stromal cells or medicinal signaling cells, are multipotent stromal cells that can Cellular differentiation, differentiate into a variety of cell types, including osteoblasts (bone cells), ...

s within

mesenchyme Mesenchyme () is a type of loosely organized animal embryonic connective tissue of undifferentiated cells that give rise to most tissues, such as skin, blood, or bone. The interactions between mesenchyme and epithelium help to form nearly ever ...

or the medullary 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 an

osteoblast Osteoblasts (from the Greek combining forms for " bone", ὀστέο-, ''osteo-'' and βλαστάνω, ''blastanō'' "germinate") are cells with a single nucleus that synthesize bone. However, in the process of bone formation, osteoblasts fu ...

. 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 The nucleolus (; : nucleoli ) is the largest structure in the cell nucleus, nucleus of eukaryote, eukaryotic cell (biology), cells. It is best known as the site of ribosome biogenesis. The nucleolus also participates in the formation of signa ...

that is surrounded by finely dispersed

chromatin Chromatin is a complex of DNA and protein found in eukaryote, eukaryotic cells. The primary function is to package long DNA molecules into more compact, denser structures. This prevents the strands from becoming tangled and also plays important r ...

particles, giving the nucleus a clear appearance; and a small amount of

Golgi apparatus The Golgi apparatus (), also known as the Golgi complex, Golgi body, or simply the Golgi, is an organelle found in most eukaryotic Cell (biology), cells. Part of the endomembrane system in the cytoplasm, it protein targeting, packages proteins ...

, rough endoplasmic reticulum,

mitochondria A mitochondrion () is an organelle found in the cells of most eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is us ...

, and polyribosomes. Furthermore, the mesenchymal stem cells are widely dispersed within an extracellular matrix that is devoid of every type of

collagen Collagen () is the main structural protein in the extracellular matrix of the connective tissues of many animals. It is the most abundant protein in mammals, making up 25% to 35% of protein content. Amino acids are bound together to form a trip ...

, except for a few reticular fibrils. The process of intramembranous ossification starts when a small group of adjacent MSCs begin to replicate and form a small, dense cluster of cells that is called a ''nidus''. 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, an osteoprogenitor cell. 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, an

. Then the osteoblasts create an extracellular matrix containing Type-I collagen fibrils, which is osteoid. 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 become

osteocyte An osteocyte, an oblate-shaped type of bone cell with dendritic processes, is the most commonly found cell in mature bone. It can live as long as the organism itself. The adult human body has about 42 billion of them. Osteocytes do not divide an ...

s. 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 rudimentary

Formation of lamellar bone

The first step in the process is the formation of bone spicules which eventually fuse with each other and become trabeculae. The

periosteum The periosteum is a membrane that covers the outer surface of all bones, except at the articular surfaces (i.e. the parts within a joint space) of long bones. (At the joints of long bones the bone's outer surface is lined with "articular cartila ...

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''.

Formation of bone spicules

Embryo An embryo ( ) is the initial stage of development for a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male sp ...

logic mesenchymal cells (MSC) condense into layers of vascularized primitive

connective tissue Connective tissue is one of the four primary types of animal tissue, a group of cells that are similar in structure, along with epithelial tissue, muscle tissue, and nervous tissue. It develops mostly from the mesenchyme, derived from the mesod ...

. Certain mesenchymal cells group together, usually near or around blood vessels, and differentiate into osteogenic cells which deposit bone

matrix Matrix (: matrices or matrixes) or MATRIX may refer to: Science and mathematics * Matrix (mathematics), a rectangular array of numbers, symbols or expressions * Matrix (logic), part of a formula in prenex normal form * Matrix (biology), the m ...

constitutively. These aggregates of bony

are called bone spicules. Separate mesenchymal cells differentiate into

s, which line up along the surface of the spicule and secrete more osteoid, which increases the size of the spicule.

Formation of trabecular bone

As the spicules continue to grow, they fuse with adjacent spicules and this results in the formation of '' trabeculae''. When

s become trapped in the matrix they secrete, they differentiate into

s. Osteoblasts continue to line up on the surface which increases the size. As growth continues, trabeculae become interconnected and ''trabecular bone'' is formed. The term ''primary spongiosa'' is also used to refer to the initial trabecular network.

Primary centre of ossification

The ''

'' is formed around the trabeculae by differentiating mesenchymal cells. The primary center of ossification is the area where bone growth occurs between the

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 osteons

Osteon In osteology, the osteon or haversian system (; named for Clopton Havers) is the fundamental functional unit of much compact bone. Osteons are roughly cylindrical structures that are typically between 0.25 mm and 0.35 mm in diameter. Thei ...

s are components or principal structures of compact bone. During the formation of bone spicules,

cytoplasmic The cytoplasm describes all the material within a eukaryotic or prokaryotic cell, enclosed by the cell membrane, including the organelles and excluding the nucleus in eukaryotic cells. The material inside the nucleus of a eukaryotic cell and ...

processes from osteoblasts interconnect. This becomes the canaliculi of osteons. Since bone spicules tend to form around

blood vessel Blood vessels are the tubular structures of a circulatory system that transport blood throughout many Animal, animals’ bodies. Blood vessels transport blood cells, nutrients, and oxygen to most of the Tissue (biology), tissues of a Body (bi ...

s, 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.

Examples in the human body

The following bones develop in humans via ''Intramembranous ossification'': * Flat bones of the face * Most of the bones of the

skull The skull, or cranium, is typically a bony enclosure around the brain of a vertebrate. In some fish, and amphibians, the skull is of cartilage. The skull is at the head end of the vertebrate. In the human, the skull comprises two prominent ...

* Clavicles Other bone that formed by intramembranous ossification are: cortices of tubular and flat bones as well as the calvaria, upper facial bones, tympanic temporal bone, vomer, and medial pterygoid process.

Footnotes

References

* {{Bone and cartilage Vertebrate developmental biology Skeletal system de:Ossifikation#Desmale Ossifikation