Ossification

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Bone is broken down by osteoclasts, and rebuilt by osteoblasts, both of which communicate through cytokine (TGF-b, IGF) signalling. Bonemetabolism.svg
Bone is broken down by osteoclasts, and rebuilt by osteoblasts, both of which communicate through cytokine (TGF-β, IGF) signalling.

Ossification (also called osteogenesis or bone mineralization) in bone remodeling is the process of laying down new bone material by cells named osteoblasts. It is synonymous with bone tissue formation. [1] There are two processes resulting in the formation of normal, healthy bone tissue: [2] Intramembranous ossification is the direct laying down of bone into the primitive connective tissue (mesenchyme), while endochondral ossification involves cartilage as a precursor.

Contents

In fracture healing, endochondral osteogenesis is the most commonly occurring process, for example in fractures of long bones treated by plaster of Paris, whereas fractures treated by open reduction and internal fixation with metal plates, screws, pins, rods and nails may heal by intramembranous osteogenesis.

Heterotopic ossification is a process resulting in the formation of bone tissue that is often atypical, at an extraskeletal location. Calcification is often confused with ossification. Calcification is synonymous with the formation of calcium-based salts and crystals within cells and tissue. It is a process that occurs during ossification, but not necessarily vice versa.

The exact mechanisms by which bone development is triggered remains unclear, but growth factors and cytokines appear to play a role.

Time period [3] Bones affected [3]
Third month of fetal developmentOssification in long bones beginning
Fourth monthMost primary ossification centers have appeared in the diaphyses of bone.
Birth to 5 yearsSecondary ossification centers appear in the epiphyses
5 years to 12 years in females, 5 to 14 years in malesOssification is spreading rapidly from the ossification centers and various bones are becoming ossified.
17 to 20 yearsBone of upper limbs and scapulae becoming completely ossified
18 to 23 yearsBone of the lower limbs and os coxae become completely ossified
23 to 26 yearsBone of the sternum, clavicles, and vertebrae become completely ossified
By 25 yearsNearly all bones are completely ossified

Intramembranous ossification

Intramembranous ossification forms the flat bones of the skull, mandible and hip bone.

Osteoblasts cluster together to create an ossification center. They then start secreting osteoid, an unmineralized collagen-proteoglycan matrix that has the ability to bind calcium. As calcium binds to the osteoid, the matrix hardens, and the osteoblasts become entrapped, transforming into osteocytes.

As osteoblasts continue to secrete osteoid, it surrounds blood vessels, leading to the formation of trabecular (cancellous or spongy) bone. These blood vessels will eventually develop into red bone marrow. Mesenchymal cells on the bone surface form a membrane known as the periosteum. Osteoblasts secrete osteoid in parallel with the existing matrix, creating layers of compact (cortical) bone. [4]

Endochondral ossification

Diagram showing stages of endochondral ossification Bone growth -- Smart-Servier (cropped).jpg
Diagram showing stages of endochondral ossification

Endochondral ossification is the formation of long bones and other bones. This requires a hyaline cartilage precursor. There are two centers of ossification for endochondral ossification.

The primary center

In long bones, bone tissue first appears in the diaphysis (middle of shaft). Chondrocytes multiply and form trebeculae. Cartilage is progressively eroded and replaced by hardened bone, extending towards the epiphysis. A perichondrium layer surrounding the cartilage forms the periosteum, which generates osteogenic cells that then go on to make a collar that encircles the outside of the bone and remodels the medullary cavity on the inside.

The nutrient artery enters via the nutrient foramen from a small opening in the diaphysis. It invades the primary center of ossification, bringing osteogenic cells (osteoblasts on the outside, osteoclasts on the inside.) The canal of the nutrient foramen is directed away from more active end of bone when one end grows more than the other. When bone grows at same rate at both ends, the nutrient artery is perpendicular to the bone.

Most other bones (e.g. vertebrae) also have primary ossification centers, and bone is laid down in a similar manner.

Secondary centers

The secondary centers generally appear at the epiphysis. Secondary ossification mostly occurs after birth (except for distal femur and proximal tibia which occurs during 9th month of fetal development). The epiphyseal arteries and osteogenic cells invade the epiphysis, depositing osteoclasts and osteoblasts which erode the cartilage and build bone, respectively. This occurs at both ends of long bones but only one end of digits and ribs.

Microscopic image of the growth plate Proximal tibia Masson Goldner Trikrom rabbit 600x growth zone.jpg
Microscopic image of the growth plate

Evolution

A spotted gar larva at 22 days stained for cartilage (blue) and bone (red). Lepisosteus oculatus larva at 22 days.png
A spotted gar larva at 22 days stained for cartilage (blue) and bone (red).

Several hypotheses have been proposed for how bone evolved as a structural element in vertebrates. One hypothesis is that bone developed from tissues that evolved to store minerals. Specifically, calcium-based minerals were stored in cartilage and bone was an exaptation development from this calcified cartilage. [5] However, other possibilities include bony tissue evolving as an osmotic barrier, or as a protective structure.

See also

Related Research Articles

<span class="mw-page-title-main">Bone</span> Rigid organs that constitute part of the endoskeleton of vertebrates

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 enable mobility. Bones come in a variety of shapes and sizes and have complex internal and external structures. They are lightweight yet strong and hard and serve multiple functions.

<span class="mw-page-title-main">Bone healing</span> Healing from bone injury

Bone healing, or fracture healing, is a proliferative physiological process in which the body facilitates the repair of a bone fracture.

<span class="mw-page-title-main">Osteoblast</span> Cells secreting extracellular matrix

Osteoblasts are cells with a single nucleus that synthesize bone. However, in the process of bone formation, osteoblasts function in groups of connected cells. Individual cells cannot make bone. A group of organized osteoblasts together with the bone made by a unit of cells is usually called the osteon.

<span class="mw-page-title-main">Osteoid</span> Unmineralized, organic portion of the bone matrix

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 it becomes mineralized, the osteoid and its adjacent bone cells have developed into new bone tissue.

<span class="mw-page-title-main">Periosteum</span> Membrane covering outer surface of bones

The periosteum is a membrane that covers the outer surface of all bones, except at the articular surfaces of long bones. Endosteum lines the inner surface of the medullary cavity of all long bones.

<span class="mw-page-title-main">Long bone</span> Bone that is longer than it is wide

The long bones are those that are longer than they are wide. They are one of five types of bones: long, short, flat, irregular and sesamoid. Long bones, especially the femur and tibia, are subjected to most of the load during daily activities and they are crucial for skeletal mobility. They grow primarily by elongation of the diaphysis, with an epiphysis at each end of the growing bone. The ends of epiphyses are covered with hyaline cartilage. The longitudinal growth of long bones is a result of endochondral ossification at the epiphyseal plate. Bone growth in length is stimulated by the production of growth hormone (GH), a secretion of the anterior lobe of the pituitary gland.

<span class="mw-page-title-main">Osteocyte</span> Mature osteoblasts which helps in communication between cells and also in molecular synthesis

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 have an average half life of 25 years. They are derived from osteoprogenitor cells, some of which differentiate into active osteoblasts. Osteoblasts/osteocytes develop in mesenchyme.

<span class="mw-page-title-main">Chondrocyte</span> Cell that makes up cartilage

Chondrocytes are the only cells found in healthy cartilage. They produce and maintain the cartilaginous matrix, which consists mainly of collagen and proteoglycans. Although the word chondroblast is commonly used to describe an immature chondrocyte, the term is imprecise, since the progenitor of chondrocytes can differentiate into various cell types, including osteoblasts.

<span class="mw-page-title-main">Endochondral ossification</span> Cartilaginous bone development that forms the long bones

Endochondral ossification is one of the two essential pathways by which bone tissue is produced during fetal development of the mammalian skeletal system, the other pathway being intramembranous ossification. Both endochondral and intramembranous processes initiate from a precursor mesenchymal tissue, but their transformations into bone are different. In intramembranous ossification, mesenchymal tissue is directly converted into bone. On the other hand, endochondral ossification starts with mesenchymal tissue turning into an intermediate cartilage stage, which is eventually substituted by bone.

<span class="mw-page-title-main">Intramembranous ossification</span> Mesenchymal bone development that forms the non-long bones

Intramembranous ossification is one of the two essential processes during fetal development of the gnathostome skeletal system by which rudimentary bone tissue is created. Intramembranous ossification is also an essential process during the natural healing of bone fractures and the rudimentary formation of bones of the head.

<span class="mw-page-title-main">Metaphysis</span> Neck portion of a long bone between the epiphysis and the diaphysis

The metaphysis is the neck portion of a long bone between the epiphysis and the diaphysis. It contains the growth plate, the part of the bone that grows during childhood, and as it grows it ossifies near the diaphysis and the epiphyses. The metaphysis contains a diverse population of cells including mesenchymal stem cells, which give rise to bone and fat cells, as well as hematopoietic stem cells which give rise to a variety of blood cells as well as bone-destroying cells called osteoclasts. Thus the metaphysis contains a highly metabolic set of tissues including trabecular (spongy) bone, blood vessels, as well as Marrow Adipose Tissue (MAT).

<span class="mw-page-title-main">Epiphyseal plate</span> Cartilage plate in the neck of a long bone

The epiphyseal plate, epiphysial plate, physis, or growth plate is a hyaline cartilage plate in the metaphysis at each end of a long bone. It is the part of a long bone where new bone growth takes place; that is, the whole bone is alive, with maintenance remodeling throughout its existing bone tissue, but the growth plate is the place where the long bone grows longer.

<span class="mw-page-title-main">Short bone</span> Bones that are as wide as they are long

Short bones are designated as those bones that are more or less equal in length, width, and thickness. They include the tarsals in the ankle and the carpals in the wrist. They are one of five types of bones: short, long, flat, irregular and sesamoid. Most short bones are named according to their shape as they exhibit a variety of complex morphological features

<span class="mw-page-title-main">Ossification center</span> Point where ossification of the cartilage begins

An ossification center is a point where ossification of the hyaline cartilage begins. The first step in ossification is that the chondrocytes at this point become hypertrophic and arrange themselves in rows.

<span class="mw-page-title-main">Sp7 transcription factor</span> Protein-coding gene in the species Homo sapiens

Transcription factor Sp7, also called osterix (Osx), is a protein that in humans is encoded by the SP7 gene. It is a member of the Sp family of zinc-finger transcription factors It is highly conserved among bone-forming vertebrate species It plays a major role, along with Runx2 and Dlx5 in driving the differentiation of mesenchymal precursor cells into osteoblasts and eventually osteocytes. Sp7 also plays a regulatory role by inhibiting chondrocyte differentiation maintaining the balance between differentiation of mesenchymal precursor cells into ossified bone or cartilage. Mutations of this gene have been associated with multiple dysfunctional bone phenotypes in vertebrates. During development, a mouse embryo model with Sp7 expression knocked out had no formation of bone tissue. Through the use of GWAS studies, the Sp7 locus in humans has been strongly associated with bone mass density. In addition there is significant genetic evidence for its role in diseases such as Osteogenesis imperfecta (OI).

<span class="mw-page-title-main">Keutel syndrome</span> Medical condition

Keutel syndrome (KS) is a rare autosomal recessive genetic disorder characterized by abnormal diffuse cartilage calcification, hypoplasia of the mid-face, peripheral pulmonary stenosis, hearing loss, short distal phalanges (tips) of the fingers and mild mental retardation. Individuals with KS often present with peripheral pulmonary stenosis, brachytelephalangism, sloping forehead, midface hypoplasia, and receding chin. It is associated with abnormalities in the gene coding for matrix gla protein, MGP. Being an autosomal recessive disorder, it may be inherited from two unaffected, abnormal MGP-carrying parents. Thus, people who inherit two affected MGP alleles will likely inherit KS.

<span class="mw-page-title-main">Osteochondroprogenitor cell</span>

Osteochondroprogenitor cells are progenitor cells that arise from mesenchymal stem cells (MSC) in the bone marrow. They have the ability to differentiate into osteoblasts or chondrocytes depending on the signalling molecules they are exposed to, giving rise to either bone or cartilage respectively. Osteochondroprogenitor cells are important for bone formation and maintenance.

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Craniofacial regeneration refers to the biological process by which the skull and face regrow to heal an injury. This page covers birth defects and injuries related to the craniofacial region, the mechanisms behind the regeneration, the medical application of these processes, and the scientific research conducted on this specific regeneration. This regeneration is not to be confused with tooth regeneration. Craniofacial regrowth is broadly related to the mechanisms of general bone healing.

Joints form during embryonic development in conjunction with the formation and growth of the associated bones. The joints and bones are developed from the embryonic tissue called mesenchyme.

References

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  2. Caetano-Lopes J, Canhão H, Fonseca JE (2007). "Osteoblasts and bone formation". Acta reumatológica portuguesa. 32 (2): 103–10. PMID   17572649.
  3. 1 2 Emily Morey-Holton. "Predicting Height from the Length of Limb Bones". Examining Effects of Space Flight on the Skeletal System. Moffett Field, California: NASA Ames Research Center. Archived from the original on 2012-03-01.
  4. Breeland, Grant; Sinkler, Margaret A.; Menezes, Ritesh G. (2024), "Embryology, Bone Ossification", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID   30969540 , retrieved 2024-05-15
  5. Donoghue PC, Sansom IJ (2002). "Origin and early evolution of vertebrate skeletonization". Microsc. Res. Tech. 59 (5): 352–72. doi: 10.1002/jemt.10217 . PMID   12430166. S2CID   10933086.