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 fish characterized by a cartilaginous skeleton, five to seven gill slits on the sides of the head, and pectoral fins that are not fused to the head. Modern sharks are classified within the clade Selachi ...

skeletal system A skeleton is the structural frame that supports the body of an animal. There are several types of skeletons, including the exoskeleton, which is the stable outer shell of an organism, the endoskeleton, which forms the support structure insid ...

by which rudimentary

bone tissue 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, and ...

is created. Intramembranous ossification is also an essential process during the natural healing of

bone fractures A bone fracture (abbreviated FRX or Fx, Fx, or #) is a medical condition in which there is a partial or complete break in the continuity of any bone in the body. In more severe cases, the bone may be broken into several fragments, known as a '' ...

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, an ...

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 animals may no ...

. Unlike

endochondral ossification Endochondral ossification is one of the two essential processes during fetal development of the mammalian skeletal system by which bone tissue is produced. Unlike intramembranous ossification, the other process by which bone tissue is produce ...

, which is the other process by which bone tissue is created during fetal development, cartilage 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 differentiate into a variety of cell types, including osteoblasts (bone cells), chondrocytes (cartilage ...

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 every ...

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 functi ...

. Before it begins to develop, the morphological characteristics of a MSC are: A small

cell body The soma (pl. ''somata'' or ''somas''), perikaryon (pl. ''perikarya''), neurocyton, or cell body is the bulbous, non-process portion of a neuron or other brain cell type, containing the cell nucleus. The word 'soma' comes from the Greek '' σῶ� ...

with a few cell processes that are long and thin; a large, round

nucleus Nucleus ( : nuclei) is a Latin word for the seed inside a fruit. It most often refers to: *Atomic nucleus, the very dense central region of an atom * Cell nucleus, a central organelle of a eukaryotic cell, containing most of the cell's DNA Nucl ...

with a prominent

nucleolus The nucleolus (, plural: nucleoli ) is the largest structure in the nucleus of eukaryotic cells. It is best known as the site of ribosome biogenesis, which is the synthesis of ribosomes. The nucleolus also participates in the formation of s ...

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 ...

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 cells. Part of the endomembrane system in the cytoplasm, it packages proteins into membrane-bound vesicles ...

rough endoplasmic reticulum The endoplasmic reticulum (ER) is, in essence, the transportation system of the eukaryotic cell, and has many other important functions such as protein folding. It is a type of organelle made up of two subunits – rough endoplasmic reticulum ( ...

, mitochondria, and

polyribosomes A polyribosome (or polysome or ergosome) is a group of ribosomes bound to an mRNA molecule like “beads” on a “thread”. It consists of a complex of an mRNA molecule and two or more ribosomes that act to translate mRNA instructions into pol ...

. Furthermore, the mesenchymal stem cells are widely dispersed within an

extracellular matrix In biology, the extracellular matrix (ECM), also called intercellular matrix, is a three-dimensional network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide struc ...

that is devoid of every type of collagen, 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 Type I collagen is the most abundant collagen of the human body. It forms large, eosinophilic fibers known as collagen fibers. It is present in scar tissue, the end product when tissue heals by repair, as well as tendons, ligaments, the end ...

fibrils, which is

osteoid In histology, osteoid is the unmineralized, organic portion of the bone matrix that forms prior to the maturation of bone tissue. Osteoblasts begin the process of forming bone tissue by secreting the osteoid as several specific proteins. When ...

. 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 and ...

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 Spicules are any of various small needle-like anatomical structures occurring in organisms Spicule may also refer to: * Spicule (sponge), small skeletal elements of sea sponges * Spicule (nematode), reproductive structures found in male nematodes ...

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. Endosteum lines the inner surface of the medullary cavity of all long bones. Struc ...

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 an initial stage of development of 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 sperm ...

logic

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

s (MSC) condense into layers of vascularized primitive

connective tissue Connective tissue is one of the four primary types of animal tissue, along with epithelial tissue, muscle tissue, and nervous tissue. It develops from the mesenchyme derived from the mesoderm the middle embryonic germ layer. Connective tissue ...

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

matrix Matrix most commonly refers to: * ''The Matrix'' (franchise), an American media franchise ** '' The Matrix'', a 1999 science-fiction action film ** "The Matrix", a fictional setting, a virtual reality environment, within ''The Matrix'' (franchi ...

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

, 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 ''

trabecula A trabecula (plural trabeculae, from Latin for "small beam") is a small, often microscopic, tissue element in the form of a small beam, strut or rod that supports or anchors a framework of parts within a body or organ. A trabecula generally has ...

e''. 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 osteon

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

cytoplasm In cell biology, the cytoplasm is all of the material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. ...

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

blood vessel Blood vessels are the structures of the circulatory system that transport blood throughout the human body. These vessels transport blood cells, nutrients, and oxygen to the tissues of the body. They also take waste and carbon dioxide away from ...

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 is a bone protective cavity for the brain. The skull is composed of four types of bone i.e., cranial bones, facial bones, ear ossicles and hyoid bone. However two parts are more prominent: the cranium and the mandible. In humans, t ...

* 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