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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.
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 development | Ossification in long bones beginning |
Fourth month | Most primary ossification centers have appeared in the diaphyses of bone. |
Birth to five years | Secondary ossification centers appear in the epiphyses |
five years to 12 years in females, 5 to 14 years in males | Ossification is spreading rapidly from the ossification centers and various bones are becoming ossified. |
17 to 20 years | Bone of upper limbs and scapulae becoming completely ossified |
18 to 23 years | Bone of the lower limbs and os coxae become completely ossified |
23 to 26 years | Bone of the sternum, clavicles, and vertebrae become completely ossified |
By 25 years | Nearly all bones are completely ossified |
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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 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.
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.
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.
Bone healing, or fracture healing, is a proliferative physiological process in which the body facilitates the repair of a bone fracture.
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.
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. The osteoid and its adjacent bone cells have developed into new bone tissue when it becomes mineralized.
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.
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.
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.
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.
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.
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.
In osteology, the osteon or haversian system 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. Their length is often hard to define, but estimates vary from several millimeters to around 1 centimeter. They are present in many bones of most mammals and some bird, reptile, and amphibian species.
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).
Chondroblasts, or perichondrial cells, is the name given to mesenchymal progenitor cells in situ which, from endochondral ossification, will form chondrocytes in the growing cartilage matrix. Another name for them is subchondral cortico-spongious progenitors. They have euchromatic nuclei and stain by basic dyes.
Flat bones are bones whose principal function is either extensive protection or the provision of broad surfaces for muscular attachment. These bones are expanded into broad, flat plates, as in the cranium (skull), the ilium, ischium, and pubis (pelvis), sternum and the rib cage. The flat bones are: the occipital, parietal, frontal, nasal, lacrimal, vomer, sternum, ribs, and scapulae.
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.
In osteology, bone remodeling or bone metabolism is a lifelong process where mature bone tissue is removed from the skeleton and new bone tissue is formed. These processes also control the reshaping or replacement of bone following injuries like fractures but also micro-damage, which occurs during normal activity. Remodeling responds also to functional demands of the mechanical loading.
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).
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.
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.
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.