osteocalcin
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Osteocalcin, also known as bone gamma-carboxyglutamic acid-containing protein (BGLAP), is a small (49-amino-acid) noncollagenous
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
hormone A hormone (from the Greek participle , "setting in motion") is a class of signaling molecules in multicellular organisms that are sent to distant organs by complex biological processes to regulate physiology and behavior. Hormones are required ...
found in bone and
dentin Dentin () (American English) or dentine ( or ) (British English) ( la, substantia eburnea) is a calcified tissue of the body and, along with enamel, cementum, and pulp, is one of the four major components of teeth. It is usually covered by ena ...
, first identified as a calcium-binding protein. Because osteocalcin has
gla domain Vitamin K-dependent carboxylation/gamma-carboxyglutamic (GLA) domain is a protein domain that contains post-translational modifications of many glutamate residues by vitamin K-dependent carboxylation to form γ-carboxyglutamate (Gla). Proteins wi ...
s, its synthesis is
vitamin K Vitamin K refers to structurally similar, fat-soluble vitamers found in foods and marketed as dietary supplements. The human body requires vitamin K for post-synthesis modification of certain proteins that are required for blood coagulation ...
dependent. In humans, osteocalcin is encoded by the ''BGLAP''
gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
. Its receptors include
GPRC6A G protein-coupled receptor family C group 6 member A (GPRC6A) is a protein that in humans is encoded by the ''GPRC6A'' gene. This protein functions as a receptor of L-α-amino acids, cations (e.g., calcium), osteocalcin, and steroids. It is a me ...
,
GPR158 Probable G-protein coupled receptor 158 is a protein that in humans is encoded by the ''GPR158'' gene. Function This protein is an orphan class C GPCR. It is highly expressed in the brain, where it binds to RGS7, an inhibitor of Gi/o-coupled ...
, and possibly a third, yet-to-be-identified receptor. There is evidence that
GPR37 Probable G-protein coupled receptor 37 is a protein that in humans is encoded by the ''GPR37'' gene. Interactions GPR37 has been shown to interact with HSPA1A and Parkin (ligase). GPR37 is a receptor for prosaposin. It was previously thought t ...
might be the third osteocalcin receptor.


Function

Osteocalcin is secreted solely by
osteoblasts Osteoblasts (from the Greek combining forms for "bone", ὀστέο-, ''osteo-'' and βλαστάνω, ''blastanō'' "germinate") are cells with a single nucleus that synthesize bone. However, in the process of bone formation, osteoblasts function ...
and thought to play a role in the body's metabolic regulation. In its
carboxylated Carboxylation is a chemical reaction in which a carboxylic acid is produced by treating a substrate with carbon dioxide. The opposite reaction is decarboxylation. In chemistry, the term carbonation is sometimes used synonymously with carboxylat ...
form it binds calcium directly and thus concentrates in bone. In its uncarboxylated form, osteocalcin acts as a
hormone A hormone (from the Greek participle , "setting in motion") is a class of signaling molecules in multicellular organisms that are sent to distant organs by complex biological processes to regulate physiology and behavior. Hormones are required ...
in the body, signalling in the pancreas, fat, muscle, testes, and brain. * In the pancreas, osteocalcin acts on beta cells, causing
beta cells Beta cells (β-cells) are a type of cell found in pancreatic islets that synthesize and secrete insulin and amylin. Beta cells make up 50–70% of the cells in human islets. In patients with Type 1 diabetes, beta-cell mass and function are dim ...
in the
pancreas The pancreas is an organ of the digestive system and endocrine system of vertebrates. In humans, it is located in the abdomen behind the stomach and functions as a gland. The pancreas is a mixed or heterocrine gland, i.e. it has both an end ...
to release more
insulin Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the ''INS'' gene. It is considered to be the main anabolic hormone of the body. It regulates the metabolism o ...
. * In
fat cells Adipocytes, also known as lipocytes and fat cells, are the cells that primarily compose adipose tissue, specialized in storing energy as fat. Adipocytes are derived from mesenchymal stem cells which give rise to adipocytes through adipogenesis. I ...
, osteocalcin triggers the release of the hormone
adiponectin Adiponectin (also referred to as GBP-28, apM1, AdipoQ and Acrp30) is a protein hormone and adipokine, which is involved in regulating glucose levels as well as fatty acid breakdown. In humans it is encoded by the ''ADIPOQ'' gene and it is produ ...
, which increases sensitivity to insulin. * In muscle, osteocalcin acts on
myocytes A muscle cell is also known as a myocyte when referring to either a cardiac muscle cell (cardiomyocyte), or a smooth muscle cell as these are both small cells. A skeletal muscle cell is long and threadlike with many nuclei and is called a muscl ...
to promote energy availability and utilization and in this manner favors exercise capacity. * In the
testes A testicle or testis (plural testes) is the male reproductive gland or gonad in all bilaterians, including humans. It is homologous to the female ovary. The functions of the testes are to produce both sperm and androgens, primarily testoster ...
, osteocalcin acts on
Leydig cell Leydig cells, also known as interstitial cells of the testes and interstitial cells of Leydig, are found adjacent to the seminiferous tubules in the testicle and produce testosterone in the presence of luteinizing hormone (LH). They are polyhedral ...
s, stimulating
testosterone Testosterone is the primary sex hormone and anabolic steroid in males. In humans, testosterone plays a key role in the development of Male reproductive system, male reproductive tissues such as testes and prostate, as well as promoting secondar ...
biosynthesis and therefore affects
male fertility Fertility is the capability to produce offspring through reproduction following the onset of sexual maturity. The fertility rate is the average number of children born by a female during her lifetime and is quantified demographically. Fertilit ...
. *In the brain, osteocalcin plays an important role in development and functioning including spatial learning and memory. An acute stress response (ASR), colloquially known as the fight-or-flight response, stimulates osteocalcin release from bone within minutes in mice, rats, and humans. Injections of high levels of osteocalcin alone can trigger an ASR in the presence of adrenal insufficiency.


Use as a biochemical marker for bone formation

As osteocalcin is produced by osteoblasts, it is often used as a marker for the bone formation process. It has been observed that higher serum osteocalcin levels are relatively well correlated with increases in
bone mineral density Bone density, or bone mineral density, is the amount of bone mineral in bone tissue. The concept is of mass of mineral per volume of bone (relating to density in the physics sense), although clinically it is measured by proxy according to optica ...
during treatment with anabolic bone formation drugs for
osteoporosis Osteoporosis is a systemic skeletal disorder characterized by low bone mass, micro-architectural deterioration of bone tissue leading to bone fragility, and consequent increase in fracture risk. It is the most common reason for a broken bone ...
, such as
teriparatide Teriparatide, sold under the brand name Forteo, is a form of parathyroid hormone (PTH) consisting of the first ( N-terminus) 34 amino acids, which is the bioactive portion of the hormone. It is an effective anabolic (promoting bone formation) ag ...
. In many studies, osteocalcin is used as a preliminary
biomarker In biomedical contexts, a biomarker, or biological marker, is a measurable indicator of some biological state or condition. Biomarkers are often measured and evaluated using blood, urine, or soft tissues to examine normal biological processes, p ...
on the effectiveness of a given drug on bone formation. For instance, one study which aimed to study the effectiveness of a
glycoprotein Glycoproteins are proteins which contain oligosaccharide chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycos ...
called
lactoferrin Lactoferrin (LF), also known as lactotransferrin (LTF), is a multifunctional protein of the transferrin family. Lactoferrin is a globular glycoprotein with a molecular mass of about 80 kDa that is widely represented in various secretory fluids, s ...
on bone formation used osteocalcin as a measure of osteoblast activity.


References


Further reading

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External links

* * {{Hormones Hormones of bone Peptide hormones