Osteonectin
Encyclopedia
Osteonectin also known as secreted protein acidic and rich in cysteine (SPARC) or basement-membrane protein 40 (BM-40) is a protein
that in humans is encoded by the SPARC gene
.
Osteonectin is a glycoprotein
in the bone
that binds sodium
. It is secreted by osteoblast
s during bone formation, initiating mineralization and promoting mineral crystal formation. Osteonectin also shows affinity for collagen
in addition to bone mineral calcium. A correlation between osteonectin over expression and ampullary cancers and chronic pancreatitis
has been found.
motif at the carboxy terminus region (domain IV).
At least the domains at the amino and carboxy terminus appear to contain calcium-binding regions.
glycoprotein that plays a vital role in bone mineralization, cell-matrix
interactions, and collagen binding. Osteonectin also increases the production and activity of matrix metalloproteinase
s, a function important to invading cancer cells within bone. Additional functions of osteonectin beneficial to tumor cells include angiogenesis
, proliferation
and migration
. Overexpression of osteonectin is reported in many human cancers such as breast, prostate and colon.
This molecule has been implicated in several biological functions, including mineralization of bone and cartilage, inhibiting mineralization, modulation of cell proliferation, facilitation of acquisition of differentiated phenotype and promotion of cell attachment and spreading.
A number of phosphoproteins and glycoproteins are found in bone. The phosphate is bound to the protein backbone through serine or threonine amino acid residues. The best characterized of these bone protein is osteonectin. It binds collagen and hydroxyapatite through separate areas of its molecule, is found in relatively large amounts in immature bone and promotes mineralization of collagen. Thus it is possible that osteonectin plays a crucial role in mineralization.
High levels of immunodetectable osteonectin are found in active osteoblasts and marrow progenitor cells, odontoblasts, periodontal ligament and gingival cells and some chondrocytes and hypertrophic chondrocytes. Osteonectin is also detectable in osteoid, bone matrix proper and dentin. Osteonectin has been localized in a variety of tissues, it is found in greatest abundance in osseous tissue, tissues characterized by high turnover (such as intestinal epithelium), basement membranes and certain neoplasms. Osteonectin is expressed by a wide variety of cells including chondrocytes, fibroblasts, platelets, endothelial cells, epithelial cells, Leydig cells, Sertoli cells, luteal cells, adrenal cortical cells and numerous neoplastic cell lines (such as SaOS-2 cells from human osteosarcoma).
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
that in humans is encoded by the SPARC gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
.
Osteonectin is a glycoprotein
Glycoprotein
Glycoproteins are proteins that contain oligosaccharide chains covalently attached to polypeptide side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycosylation. In proteins that have segments extending...
in the bone
Bone
Bones are rigid organs that constitute part of the endoskeleton of vertebrates. They support, and protect the various organs of the body, produce red and white blood cells and store minerals. Bone tissue is a type of dense connective tissue...
that binds sodium
Sodium
Sodium is a chemical element with the symbol Na and atomic number 11. It is a soft, silvery-white, highly reactive metal and is a member of the alkali metals; its only stable isotope is 23Na. It is an abundant element that exists in numerous minerals, most commonly as sodium chloride...
. It is secreted by osteoblast
Osteoblast
Osteoblasts are mononucleate cells that are responsible for bone formation; in essence, osteoblasts are specialized fibroblasts that in addition to fibroblastic products, express bone sialoprotein and osteocalcin.Osteoblasts produce a matrix of osteoid, which is composed mainly of Type I collagen...
s during bone formation, initiating mineralization and promoting mineral crystal formation. Osteonectin also shows affinity for collagen
Collagen
Collagen is a group of naturally occurring proteins found in animals, especially in the flesh and connective tissues of mammals. It is the main component of connective tissue, and is the most abundant protein in mammals, making up about 25% to 35% of the whole-body protein content...
in addition to bone mineral calcium. A correlation between osteonectin over expression and ampullary cancers and chronic pancreatitis
Pancreatitis
Pancreatitis is inflammation of the pancreas. It occurs when pancreatic enzymes that digest food are activated in the pancreas instead of the small intestine. It may be acute – beginning suddenly and lasting a few days, or chronic – occurring over many years...
has been found.
Gene
The human SPARC gene is 26.5 kb long, and contains 10 exons and 9 introns and is located on chromosome 5q31-q33.Structure
Osteonectin is a glycoprotein of 40 kD. Osteonectin is an acidic, cysteine-rich glycoprotein consisting of a single polypeptide chain that can be broken into 4 domains: 1) an Ca++ binding domains near the glutamic acidic-rich region at the amino terminus (domain I) , 2) a cysteine- rich (domain II), 3) a hydrophilic region (domain III) and 4) an EF handEF hand
The EF hand is a helix-loop-helix structural domain found in a large family of calcium-binding proteins. The EF-hand motif contains a helix-loop-helix topology, much like the spread thumb and forefinger of the human hand, in which the Ca2+ ions are coordinated by ligands within the loop...
motif at the carboxy terminus region (domain IV).
At least the domains at the amino and carboxy terminus appear to contain calcium-binding regions.
Function
Osteonectin is an acidic, secreted extracellular matrixExtracellular matrix
In biology, the extracellular matrix is the extracellular part of animal tissue that usually provides structural support to the animal cells in addition to performing various other important functions. The extracellular matrix is the defining feature of connective tissue in animals.Extracellular...
glycoprotein that plays a vital role in bone mineralization, cell-matrix
Cell junction
A cell junction is a type of structure that exists within the tissue of a some multicellular organism . Cell junctions consist of protein complexes and provide contact between neighbouring cells or between a cell and the extracellular matrix...
interactions, and collagen binding. Osteonectin also increases the production and activity of matrix metalloproteinase
Matrix metalloproteinase
Matrix metalloproteinases are zinc-dependent endopeptidases; other family members are adamalysins, serralysins, and astacins. The MMPs belong to a larger family of proteases known as the metzincin superfamily....
s, a function important to invading cancer cells within bone. Additional functions of osteonectin beneficial to tumor cells include angiogenesis
Angiogenesis
Angiogenesis is the physiological process involving the growth of new blood vessels from pre-existing vessels. Though there has been some debate over terminology, vasculogenesis is the term used for spontaneous blood-vessel formation, and intussusception is the term for the formation of new blood...
, proliferation
Cell growth
The term cell growth is used in the contexts of cell development and cell division . When used in the context of cell division, it refers to growth of cell populations, where one cell grows and divides to produce two "daughter cells"...
and migration
Cell migration
Cell migration is a central process in the development and maintenance of multicellular organisms. Tissue formation during embryonic development, wound healing and immune responses all require the orchestrated movement of cells in particular directions to specific locations...
. Overexpression of osteonectin is reported in many human cancers such as breast, prostate and colon.
This molecule has been implicated in several biological functions, including mineralization of bone and cartilage, inhibiting mineralization, modulation of cell proliferation, facilitation of acquisition of differentiated phenotype and promotion of cell attachment and spreading.
A number of phosphoproteins and glycoproteins are found in bone. The phosphate is bound to the protein backbone through serine or threonine amino acid residues. The best characterized of these bone protein is osteonectin. It binds collagen and hydroxyapatite through separate areas of its molecule, is found in relatively large amounts in immature bone and promotes mineralization of collagen. Thus it is possible that osteonectin plays a crucial role in mineralization.
Tissue distribution
Fibroblasts, including periodontal fibroblasts, synthesize osteonectin. This protein is synthesized by macrophages at sites of wound repair and platelet degranulation.so it may play a important role in wound healing. SPARC does not support cell attachment and like thrombospondin and tenascin, it antiadhesive and an inhibitor of cell spreading. It distrupt focal adhesion in fibroblasts. Also regulates the proliferation of some cells especially the endothelial cells, and it mediate this effect through its ability to bind to cytokines and growth factors. Osteonectin has also been found decrease DNA synthesis in cultured bone.High levels of immunodetectable osteonectin are found in active osteoblasts and marrow progenitor cells, odontoblasts, periodontal ligament and gingival cells and some chondrocytes and hypertrophic chondrocytes. Osteonectin is also detectable in osteoid, bone matrix proper and dentin. Osteonectin has been localized in a variety of tissues, it is found in greatest abundance in osseous tissue, tissues characterized by high turnover (such as intestinal epithelium), basement membranes and certain neoplasms. Osteonectin is expressed by a wide variety of cells including chondrocytes, fibroblasts, platelets, endothelial cells, epithelial cells, Leydig cells, Sertoli cells, luteal cells, adrenal cortical cells and numerous neoplastic cell lines (such as SaOS-2 cells from human osteosarcoma).