Osteocalcin

Last updated
BGLAP
Osteocalcin 1Q8H.png
Identifiers
Aliases BGLAP , BGP, OC, OCN, bone gamma-carboxyglutamate protein, Osteocalcin
External IDs OMIM: 112260 MGI: 88155 HomoloGene: 104130 GeneCards: BGLAP
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_199173

NM_031368
NM_001305448
NM_001305449
NM_001305450

RefSeq (protein)

NP_954642

NP_001292377
NP_001292378
NP_001292379
NP_112736

Location (UCSC) Chr 1: 156.24 – 156.24 Mb Chr 3: 88.28 – 88.28 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Osteocalcin, also known as bone gamma-carboxyglutamic acid-containing protein (BGLAP), is a small (49-amino-acid [5] ) noncollagenous protein hormone found in bone and dentin, first identified as a calcium-binding protein. [6]

Contents

Because osteocalcin has gla domains, its synthesis is vitamin K dependent. In humans, osteocalcin is encoded by the BGLAP gene. [7] [8] Its receptors include GPRC6A, GPR158, and possibly a third, yet-to-be-identified receptor. [9] [10] There is evidence that GPR37 might be the third osteocalcin receptor. [11]

Function

Osteocalcin is secreted solely by osteoblasts and thought to play a role in the body's metabolic regulation. [12] In its carboxylated form it binds calcium directly and thus concentrates in bone.

In its uncarboxylated form, osteocalcin acts as a hormone in the body, signalling in the pancreas, fat, muscle, testes, and brain. [13]

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. [18]

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 during treatment with anabolic bone formation drugs for osteoporosis, such as teriparatide. In many studies, osteocalcin is used as a preliminary biomarker on the effectiveness of a given drug on bone formation. For instance, one study which aimed to study the effectiveness of a glycoprotein called lactoferrin on bone formation used osteocalcin as a measure of osteoblast activity. [19]

Related Research Articles

<span class="mw-page-title-main">Osteoblast</span> Cells secreting extracellular matrix

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.

<span class="mw-page-title-main">Parathyroid hormone-related protein</span> Mammalian protein

Parathyroid hormone-related protein (PTHrP) is a proteinaceous hormone and a member of the parathyroid hormone family secreted by mesenchymal stem cells. It is occasionally secreted by cancer cells. However, it also has normal functions in bone, teeth, vascular tissues and other tissues.

<span class="mw-page-title-main">Adipocyte</span> Cells that primarily compose adipose tissue, specialized in storing energy as fat

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. In cell culture, adipocyte progenitors can also form osteoblasts, myocytes and other cell types.

<span class="mw-page-title-main">Osteoprotegerin</span> Mammalian protein found in Homo sapiens

Osteoprotegerin (OPG), also known as osteoclastogenesis inhibitory factor (OCIF) or tumour necrosis factor receptor superfamily member 11B (TNFRSF11B), is a cytokine receptor of the tumour necrosis factor (TNF) receptor superfamily encoded by the TNFRSF11B gene.

<span class="mw-page-title-main">Osteocyte</span> Mature osteoblasts which helps in communication between cells and also in molecular synthesis

An osteocyte, an oblate shaped type of bone cell with dendritic processes, is the most commonly found cell in mature bone. It can live as long as the organism itself. The adult human body has about 42 billion of them. Osteocytes do not divide and have an average half life of 25 years. They are derived from osteoprogenitor cells, some of which differentiate into active osteoblasts. Osteoblasts/osteocytes develop in mesenchyme.

<span class="mw-page-title-main">Klotho (biology)</span> Human enzyme

Klotho is an enzyme that in humans is encoded by the KL gene. The three subfamilies of klotho are α-klotho, β-klotho, and γ-klotho. α-klotho activates FGF23, and β-klotho activates FGF19 and FGF21. When the subfamily is not specified, the word "klotho" typically refers to the α-klotho subfamily, because α-klotho was discovered before the other members.

<span class="mw-page-title-main">Osteopontin</span> Mammalian protein found in Homo sapiens

Osteopontin (OPN), also known as bone /sialoprotein I, early T-lymphocyte activation (ETA-1), secreted phosphoprotein 1 (SPP1), 2ar and Rickettsia resistance (Ric), is a protein that in humans is encoded by the SPP1 gene. The murine ortholog is Spp1. Osteopontin is a SIBLING (glycoprotein) that was first identified in 1986 in osteoblasts.

<span class="mw-page-title-main">Sclerostin</span> Protein-coding gene in the species Homo sapiens

Sclerostin is a protein that in humans is encoded by the SOST gene. It is a secreted glycoprotein with a C-terminal cysteine knot-like (CTCK) domain and sequence similarity to the DAN family of bone morphogenetic protein (BMP) antagonists. Sclerostin is produced primarily by the osteocyte but is also expressed in other tissues, and has anti-anabolic effects on bone formation.

<span class="mw-page-title-main">TRPV6</span> Protein-coding gene in the species Homo sapiens

TRPV6 is a membrane calcium (Ca2+) channel protein which is particularly involved in the first step in Ca2+absorption in the intestine.

<span class="mw-page-title-main">Follistatin</span> Mammalian protein found in Homo sapiens

Follistatin, also known as activin-bindings protein, is a protein that in humans is encoded by the FST gene. Follistatin is an autocrine glycoprotein that is expressed in nearly all tissues of higher animals.

<span class="mw-page-title-main">RUNX2</span> Protein-coding gene in humans

Runt-related transcription factor 2 (RUNX2) also known as core-binding factor subunit alpha-1 (CBF-alpha-1) is a protein that in humans is encoded by the RUNX2 gene. RUNX2 is a key transcription factor associated with osteoblast differentiation.

<span class="mw-page-title-main">Bone sialoprotein</span> Protein-coding gene in the species Homo sapiens

Bone sialoprotein (BSP) is a component of mineralized tissues such as bone, dentin, cementum and calcified cartilage. BSP is a significant component of the bone extracellular matrix and has been suggested to constitute approximately 8% of all non-collagenous proteins found in bone and cementum. BSP, a SIBLING protein, was originally isolated from bovine cortical bone as a 23-kDa glycopeptide with high sialic acid content.

<span class="mw-page-title-main">KiSS1-derived peptide receptor</span> Mammalian protein found in Homo sapiens

The KiSS1-derived peptide receptor is a G protein-coupled receptor which binds the peptide hormone kisspeptin (metastin). Kisspeptin is encoded by the metastasis suppressor gene KISS1, which is expressed in a variety of endocrine and gonadal tissues. Activation of the kisspeptin receptor is linked to the phospholipase C and inositol trisphosphate second messenger cascades inside the cell.

<span class="mw-page-title-main">Parathyroid hormone 1 receptor</span> Protein-coding gene in the species Homo sapiens

Parathyroid hormone/parathyroid hormone-related peptide receptor, also known as parathyroid hormone 1 receptor (PTH1R), is a protein that in humans is encoded by the PTH1R gene. PTH1R functions as a receptor for parathyroid hormone (PTH) and for parathyroid hormone-related protein (PTHrP), also called parathyroid hormone-like hormone (PTHLH).

<span class="mw-page-title-main">GPRC6A</span> Protein-coding gene in the species Homo sapiens

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, osteocalcin, and steroids. It is a membrane androgen receptor.

<span class="mw-page-title-main">LRP5</span> Protein-coding gene in the species Homo sapiens

Low-density lipoprotein receptor-related protein 5 is a protein that in humans is encoded by the LRP5 gene. LRP5 is a key component of the LRP5/LRP6/Frizzled co-receptor group that is involved in canonical Wnt pathway. Mutations in LRP5 can lead to considerable changes in bone mass. A loss-of-function mutation causes osteoporosis pseudoglioma syndrome with a decrease in bone mass, while a gain-of-function mutation causes drastic increases in bone mass.

<span class="mw-page-title-main">DMP1</span> Protein-coding gene in the species Homo sapiens

Dentin matrix acidic phosphoprotein 1 is a protein that in humans is encoded by the DMP1 gene.

<span class="mw-page-title-main">Sp7 transcription factor</span> 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 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).

<span class="mw-page-title-main">Adipogenesis</span>

Adipogenesis is the formation of adipocytes from stem cells. It involves 2 phases, determination, and terminal differentiation. Determination is mesenchymal stem cells committing to the adipocyte precursor cells, also known as lipoblasts or preadipocytes which lose the potential to differentiate to other types of cells such as chondrocytes, myocytes, and osteoblasts. Terminal differentiation is that preadipocytes differentiate into mature adipocytes. Adipocytes can arise either from preadipocytes resident in adipose tissue, or from bone-marrow derived progenitor cells that migrate to adipose tissue.

<span class="mw-page-title-main">Bone marrow adipose tissue</span>

Bone marrow adipose tissue (BMAT), sometimes referred to as marrow adipose tissue (MAT), is a type of fat deposit in bone marrow. It increases in states of low bone density -osteoporosis, anorexia nervosa/caloric restriction, skeletal unweighting such as that which occurs in space travel, and anti-diabetes therapies. BMAT decreases in anaemia, leukaemia, and hypertensive heart failure; in response to hormones such as oestrogen, leptin, and growth hormone; with exercise-induced weight loss or bariatric surgery; in response to chronic cold exposure; and in response to pharmacological agents such as bisphosphonates, teriparatide, and metformin.

References

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  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000074489 - Ensembl, May 2017
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  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
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  6. Hauschka PV, Reid ML (August 1978). "Timed appearance of a calcium-binding protein containing gamma-carboxyglutamic acid in developing chick bone". Developmental Biology. 65 (2): 426–34. doi:10.1016/0012-1606(78)90038-6. PMID   680371.
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  8. Cancela L, Hsieh CL, Francke U, Price PA (September 1990). "Molecular structure, chromosome assignment, and promoter organization of the human matrix Gla protein gene". The Journal of Biological Chemistry. 265 (25): 15040–8. doi: 10.1016/S0021-9258(18)77221-9 . PMID   2394711.
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Further reading