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 residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
hormone
A hormone (from the Ancient Greek, Greek participle , "setting in motion") is a class of cell signaling, signaling molecules in multicellular organisms that are sent to distant organs or tissues by complex biological processes to regulate physio ...
found in bone and
dentin
Dentin ( ) (American English) or dentine ( or ) (British English) () is a calcified tissue (biology), tissue of the body and, along with tooth enamel, enamel, cementum, and pulp (tooth), pulp, is one of the four major components of teeth. It i ...
, first identified as a calcium-binding protein.
Because osteocalcin has
gla domains, its synthesis is
vitamin K2-dependent. In humans, osteocalcin is encoded by the ''BGLAP''
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
.
Its receptors include
GPRC6A,
GPR158, and possibly a third, yet-to-be-identified receptor.
There is evidence that
GPR37 might be the third osteocalcin receptor.
Function
Osteocalcin is secreted solely by
osteoblasts and is thought to play a role in the body's metabolic regulation.
In its
carboxylated form, calcium is bound directly to the bone and thus concentrates here.
In its uncarboxylated form, osteocalcin acts as a
hormone
A hormone (from the Ancient Greek, Greek participle , "setting in motion") is a class of cell signaling, signaling molecules in multicellular organisms that are sent to distant organs or tissues by complex biological processes to regulate physio ...
in the body, signalling in the pancreas, fat, muscle, testes, and brain.
* In the pancreas, osteocalcin acts on beta cells, causing
beta cells in the
pancreas
The pancreas (plural pancreases, or pancreata) is an Organ (anatomy), organ of the Digestion, digestive system and endocrine system of vertebrates. In humans, it is located in the abdominal cavity, abdomen behind the stomach and functions as a ...
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 insulin (''INS)'' gene. It is the main Anabolism, anabolic hormone of the body. It regulates the metabol ...
.
* In
fat cells, osteocalcin triggers the release of the
adiponectin hormone, which increases insulin sensitivity.
* In muscle, osteocalcin acts on
myocyte
A muscle cell, also known as a myocyte, is a mature contractile Cell (biology), cell in the muscle of an animal. In humans and other vertebrates there are three types: skeletal muscle, skeletal, smooth muscle, smooth, and Cardiac muscle, cardiac ...
s to promote energy availability and utilization and, in this manner, favors exercise capacity.
* In the
testes, osteocalcin acts on
Leydig cells, stimulating
testosterone
Testosterone is the primary male sex hormone and androgen in Male, males. In humans, testosterone plays a key role in the development of Male reproductive system, male reproductive tissues such as testicles and prostate, as well as promoting se ...
biosynthesis and affecting
male fertility.
*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 osteoblasts produce osteocalcin, it is often used as a marker for the
bone formation process. Higher serum osteocalcin levels have been observed to correlate relatively well with increases in
bone mineral density 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 more porous bone, and consequent increase in Bone fracture, fracture risk.
It is the most common reason f ...
, such as
teriparatide. 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, ...
for the effectiveness of a given drug on bone formation. For instance, one study that aimed to study the efficacy of a
glycoprotein called
lactoferrin
Lactoferrin (LF), also known as lactotransferrin (LTF), is a multifunctional protein of the transferrin family. Lactoferrin is a globular proteins, globular glycoprotein with a molecular mass of about 80 Atomic mass unit, kDa that is widely repre ...
on bone formation used osteocalcin to measure osteoblast activity.
References
Further reading
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External links
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{{Hormones
Hormones of bone
Peptide hormones