Endochondral ossification | |
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Anatomical terminology |
Endochondral ossification [1] [2] 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. [3]
Endochondral ossification is responsible for development of most bones including long and short bones, [4] the bones of the axial (ribs and vertebrae) and the appendicular skeleton (e.g. upper and lower limbs), [5] the bones of the skull base (including the ethmoid and sphenoid bones) [6] and the medial end of the clavicle. [7] In addition, endochondral ossification is not exclusively confined to embryonic development; it also plays a crucial role in the healing of fractures. [3]
The initiation of endochondral ossification starts by proliferation and condensation of mesenchymal cells in the area where the bone will eventually be formed. Subsequently, these mesenchymal progenitor cells differentiate into chondroblasts, which actively synthesize cartilage matrix components. Thus, the initial hyaline cartilage template is formed, which has the same basic shape and outline as the future bone. [8]
Interstitial growth | Appositional growth | |
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Cellular protagonists | Chondrocytes present within the existing cartilage. | Chondroblasts that develop from the perichondrium. |
Mechanism | Chondrocytes proliferate and lay down matrix. | Chondroblasts differentiate into chondrocytes and lay down matrix. |
Site of expansion | From within. | From the external surface of existing cartilage. |
Outcome | Increase in length. | Increase in width and thickness. |
In developing bones, ossification commences within the primary ossification center located in the center of the diaphysis (bone shaft), [5] where the following changes occur:
During the postnatal life, a secondary ossification center appears in each end (epiphysis) of long bones. In these secondary centers, cartilage is converted to bone similarly to that occurring in a primary ossification center. [8] As the secondary ossification centers enlarge, residual cartilage persists in two distinct locations: [11]
At the end of an individual’s growth period, the production of new cartilage in the epiphyseal plate stops. After this point, existing cartilage within the plate turns into mature bone tissue. [8]
During endochondral ossification, five distinct zones can be seen at the light-microscope level: [3]
Name | Definition |
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Zone of resting cartilage | This zone contains normal, resting hyaline cartilage. |
Zone of proliferation / cell columns | In this zone, chondrocytes undergo rapid mitosis, forming distinctive looking columns. |
Zone of maturation / hypertrophy | In this zone, the chondrocytes undergo hypertrophy (become enlarged). Chondrocytes contain large amounts of glycogen and begin to secrete vascular endothelial growth factor to initiate vascular invasion. |
Zone of calcification | In this zone, chondrocytes are either dying or dead, leaving cavities that will later become invaded by bone-forming cells. Chondrocytes here die when they can no longer receive nutrients or eliminate wastes via diffusion. This is because the calcified matrix is much less hydrated than hyaline cartilage. |
Zone of ossification | Osteoprogenitor cells invade the area and differentiate into osteoblasts, which elaborate matrix that becomes calcified on the surface of calcified cartilage. |
For complete recovery of a fractured bone’s biomechanical functionality, the bone healing process needs to culminate in the formation of lamellar bone at the fracture site to withstand the same forces and stresses it did before the fracture. Indirect fracture healing, the most common type of bone repair, [10] relies heavily on endochondral ossification. In this type of healing, endochondral ossification occurs within the fracture gap and external to the periosteum. In contrast, intramembranous ossification takes place directly beneath the periosteum, adjacent to the broken bone’s ends. [10] [12]
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.
Cartilage is a resilient and smooth type of connective tissue. It is a semi-transparent and non-porous type of tissue. 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 as articular cartilage, and is a structural component of many body parts including the rib cage, the neck and the bronchial tubes, and the intervertebral discs. In other taxa, such as chondrichthyans, but also in cyclostomes, it may constitute a much greater proportion of the skeleton. It is not as hard and rigid as bone, but it is much stiffer and much less flexible than muscle. The matrix of cartilage is made up of glycosaminoglycans, proteoglycans, collagen fibers and, sometimes, elastin. It usually grows quicker than bone.
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.
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.
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.
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.
Ossification in bone remodeling is the process of laying down new bone material by cells named osteoblasts. It is synonymous with bone tissue formation. There are two processes resulting in the formation of normal, healthy bone tissue: Intramembranous ossification is the direct laying down of bone into the primitive connective tissue (mesenchyme), while endochondral ossification involves cartilage as a precursor.
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.
The epiphyseal 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.
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
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.
A Salter–Harris fracture is a fracture that involves the epiphyseal plate of a bone, specifically the zone of provisional calcification. It is thus a form of child bone fracture. It is a common injury found in children, occurring in 15% of childhood long bone fractures. This type of fracture and its classification system is named for Robert B. Salter and William H. Harris who created and published this classification system in the Journal of Bone and Joint Surgery in 1963.
Chondroblastoma is a rare, benign, locally aggressive bone tumor that typically affects the epiphyses or apophyses of long bones. It is thought to arise from an outgrowth of immature cartilage cells (chondroblasts) from secondary ossification centers, originating from the epiphyseal plate or some remnant of it.
An isogenous group is a cluster of up to eight chondrocytes found in hyaline and elastic cartilage.
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).
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.
Orthopedic surgery is the branch of surgery concerned with conditions involving the musculoskeletal system. Orthopedic surgeons use both surgical and nonsurgical means to treat musculoskeletal injuries, sports injuries, degenerative diseases, infections, bone tumours, and congenital limb deformities. Trauma surgery and traumatology is a sub-specialty dealing with the operative management of fractures, major trauma and the multiply-injured patient.
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.
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