Chondrocalcin

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Chondrocalcin comes from a family of pro-collagen molecules. This protein is found in the bone and is involved in calcium-binding, which occurs in order to harden (or calcify) the cartilage. Another one of its roles is to assemble the triple collagen helix, which is predominately entails the linkage of glycine and proline amino acids and then the twisting of those linkages. Chondrocalcin is important because cartilage calcification of the growth plate is one of the main occurrences in endochondral bone formation. Because of its importance, it is one of the most highly created polypeptides in human cartilage. This calcium-binding protein comes from chondrocytes, which are cells that produce and maintain cartilage. Some examples of chondrocytes include collagen and proteoglycans. The chondrocytes that produce chondrocalcin are typically found in growing bone matrices that have not yet matured. These immature bone matrices are found in the epiphyseal plate at both the lower hypertrophic zone and the longitudinal septa of the cartilaginous matrix. One study was conducted on fetal cartilage discovered that the chondrocalcin protein exists as a dimer with 35,000 g/mol subunits. The reason why fetal cartilage was used is because chondrocalcin cannot be detected in mature bone. Another investigation was conducted to determine the mechanism behind calcium binding in chondrocalcin. It was discovered that along with cartilage building, the protein also had a role in cartilage destruction. [1] [2] [3] [4] [5]

Protein biological molecule consisting of chains of amino acid residues

Proteins are large biomolecules, or macromolecules, consisting of one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, responding to stimuli, providing structure to cells and organisms, and transporting molecules from one location to another. Proteins differ from one another primarily in their sequence of amino acids, which is dictated by the nucleotide sequence of their genes, and which usually results in protein folding into a specific three-dimensional structure that determines its activity.

Bone rigid organs that constitute part of the endoskeleton of vertebrates

A bone is a rigid organ that constitutes part of the vertebrate skeleton. Bones protect the various 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 a complex internal and external structure. They are lightweight yet strong and hard, and serve multiple functions.

Cartilage resilient and smooth elastic tissue, rubber-like padding that covers and protects the ends of long bones at the joints

Cartilage is a resilient and smooth elastic tissue, a rubber-like padding that covers and protects the ends of long bones at the joints, and is a structural component of the rib cage, the ear, the nose, the bronchial tubes, the intervertebral discs, and many other body components. 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.

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Osteoblast osteoblast

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 biology, matrix is the material in animal or plant cells, in which more specialized structures are embedded, and a specific part of the mitochondrion. The internal structure of connective tissues is an extracellular matrix. Finger nails and toenails grow from matrices. It is found in various connective tissue. It is generally used as a jelly like structure instead of cytoplasm in connective tissue.

Chondrocyte

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 Replacement ossification wherein bone tissue replaces cartilage.

Endochondral ossification is one of the two essential processes during fetal development of the mammalian skeletal system by which bone tissue is created. Unlike intramembranous ossification, which is the other process by which bone tissue is created, cartilage is present during endochondral ossification. Endochondral ossification is also an essential process during the rudimentary formation of long bones, the growth of the length of long bones, and the natural healing of bone fractures.

Ossification The formation of bone or of a bony substance, or the conversion of fibrous tissue or of cartilage into bone or a bony substance.

Ossification in bone remodeling is the process of laying down new bone material by cells called 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. 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.

Chondroblast

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. These cells are extremely important in Chondrogenesis due to their role in forming both the Chondrocytes and cartilage matrix which will eventually form cartilage. Use of the term is technically inaccurate since mesenchymal progenitors can also technically differentiate into osteoblasts or fat. Chondroblasts are called Chondrocytes when they embed themselves in the cartilage matrix, consisting of proteoglycan and collagen fibers, until they lie in the matrix lacunae. Once they embed themselves into the cartilage matrix, they grow the cartilage matrix by growing more cartilage extracellular matrix rather than by dividing further.

Chondrogenesis

Chondrogenesis is the process by which cartilage is developed.

Articular cartilage, most notably that which is found in the knee joint, is generally characterized by very low friction, high wear resistance, and poor regenerative qualities. It is responsible for much of the compressive resistance and load bearing qualities of the knee joint and, without it, walking is painful to impossible. Osteoarthritis is a common condition of cartilage failure that can lead to limited range of motion, bone damage and invariably, pain. Due to a combination of acute stress and chronic fatigue, osteoarthritis directly manifests itself in a wearing away of the articular surface and, in extreme cases, bone can be exposed in the joint. Some additional examples of cartilage failure mechanisms include cellular matrix linkage rupture, chondrocyte protein synthesis inhibition, and chondrocyte apoptosis. There are several different repair options available for cartilage damage or failure.

Epiphyseal plate part of a long bone where growth takes place

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.

Osteonectin protein-coding gene in the species Homo sapiens

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Pseudoachondroplasia osteochondrodysplasia that has material basis in mutations in the COMP gene which results in short limb dwarfism

Pseudoachondroplasia is an inherited disorder of bone growth. It is a genetic autosomal dominant disorder. It is generally not discovered until 2-3 years of age, since growth is normal at first. Pseudoachondroplasia is usually first detected by a drop of linear growth in contrast to peers, a curious, waddling gait or arising lower limb deformities.

Chondroblastoma Human disease

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.

Cartilage oligomeric matrix protein protein-coding gene in the species Homo sapiens

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Matrix gla protein protein-coding gene in the species Homo sapiens

Matrix gla protein (MGP) is member of a family of vitamin-K2 dependent, Gla-containing proteins. MGP has a high affinity binding to calcium ions, similar to other Gla-containing proteins. The protein acts as an inhibitor of vascular mineralization and plays a role in bone organization.

Collagen, type X, alpha 1 protein-coding gene in the species Homo sapiens

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Sp7 transcription factor 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 veterbrate 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 Keutel syndrome is characterised by diffuse cartilage calcification, brachytelephalangism, peripheral pulmonary artery stenoses and facial dysmorphism

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 genes will likely inherit KS.

Artificial cartilage is a synthetic material made of hydrogels or polymers that aims to mimic the functional properties of natural cartilage in the human body. Tissue engineering principles are used in order to create a non-degradable and biocompatible material that can replace cartilage. While creating a useful synthetic cartilage material, certain challenges need to be overcome. First, cartilage is an avascular structure in the body and therefore does not repair itself. This creates issues in regeneration of the tissue. Synthetic cartilage also needs to be stably attached to its underlying surface, bone. Lastly, in the case of creating synthetic cartilage to be used in joint spaces, high mechanical strength under compression needs to be an intrinsic property of the material.

References

  1. Hall, Brian. "Bones and Cartilage: Developmental and Evolutionary Skeletal Biology", Academic Press, 11 August 2005.
  2. Poole AR et al. "Chondrocalcin and the calcification of cartilage. A review., Clin Orthop Relat Res., July 1986. Retrieved on 27 November 2017.
  3. Poole AR et al. "The association of a newly discovered protein, called chondrocalcin, with cartilage calcification., Acta Biol Hung., 1984. Retrieved on 27 November 2017.
  4. Claudie Bantsimba-Malanda et al. "Chondrocalcin is internalized by chondrocytes and triggers cartilage destruction via an interleukin-1β-dependent pathway, Matrix Biology, November 2013. Retrieved on 27 November 2017.
  5. Poole AR et al. "Association of an Extracellular Protein (Chondrocalcin) with the Calcification of Cartilage in Endochondral Bone Formation, Journal of Cell Biology., January 1984. Retrieved on 27 November 2017.