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{{protein
{{Infobox_gene}}
|Name=bone gamma-carboxyglutamate (gla) protein (osteocalcin)
{{Distinguish|Osteonectin|Osteopontin}}
|caption=
'''Osteocalcin''', also known as '''bone gamma-carboxyglutamic acid-containing protein''' ('''BGLAP'''), is a noncollagenous [[protein]] [[hormone]] found in bone and [[dentin]]. Because it has [[gla domain]]s, its synthesis is [[vitamin K]] dependent. In humans, the osteocalcin is encoded by the ''BGLAP'' [[gene]].<ref name="pmid2785029">{{cite journal | vauthors = Puchacz E, Lian JB, Stein GS, Wozney J, Huebner K, Croce C | title = Chromosomal localization of the human osteocalcin gene | journal = Endocrinology | volume = 124 | issue = 5 | pages = 2648–50 | date = May 1989 | pmid = 2785029 | doi = 10.1210/endo-124-5-2648 }}</ref><ref name="pmid2394711">{{cite journal | vauthors = Cancela L, Hsieh CL, Francke U, Price PA | title = Molecular structure, chromosome assignment, and promoter organization of the human matrix Gla protein gene | journal = The Journal of Biological Chemistry | volume = 265 | issue = 25 | pages = 15040–8 | date = Sep 1990 | pmid = 2394711 | doi = }}</ref> Its receptor is [[GPRC6A]].<ref name="Pi_2011">{{cite journal | vauthors = Pi M, Wu Y, Quarles LD | title = GPRC6A mediates responses to osteocalcin in β-cells in vitro and pancreas in vivo | journal = Journal of Bone and Mineral Research | volume = 26 | issue = 7 | pages = 1680–1683 | date = Jul 2011 | pmid = 21425331 | doi = 10.1002/jbmr.390 | pmc = 5079536 }}</ref>
|image=
|width=
|HGNCid=1043
|Symbol=BGLAP
|AltSymbols=
|EntrezGene=632
|OMIM=112260
|RefSeq=NM_199173
|UniProt=P02818
|PDB=
|ECnumber=
|Chromosome=1
|Arm=q
|Band=25
|LocusSupplementaryData=-q31
}}
{{SI}}
{{GS}}


== Function ==


Osteocalcin is secreted solely by [[osteoblasts]] and thought to play a role in the body's metabolic regulation and is pro-osteoblastic, or bone-building, by nature.<ref name="Lee_2007"/> It is also implicated in bone mineralization and calcium ion homeostasis. Osteocalcin acts as a [[hormone]] in the body, causing [[beta cells]] in the [[pancreas]] to release more [[insulin]], and at the same time directing [[fat cells]] to release the hormone [[adiponectin]], which increases sensitivity to insulin.<ref name="Lee_2007">{{cite journal | vauthors = Lee NK, Sowa H, Hinoi E, Ferron M, Ahn JD, Confavreux C, Dacquin R, Mee PJ, McKee MD, Jung DY, Zhang Z, Kim JK, Mauvais-Jarvis F, Ducy P, Karsenty G | title = Endocrine regulation of energy metabolism by the skeleton | journal = Cell | volume = 130 | issue = 3 | pages = 456–69 | date = Aug 2007 | pmid = 17693256 | pmc = 2013746 | doi = 10.1016/j.cell.2007.05.047 }}</ref>


==Overview==
Osteocalcin acts on [[Leydig cell]]s of the [[testis]] to stimulate [[testosterone]] biosynthesis and therefore affect [[male fertility]].<ref name="pmid24145129">{{cite journal | vauthors = Karsenty G, Oury F | title = Regulation of male fertility by the bone-derived hormone osteocalcin | journal = Molecular and Cellular Endocrinology | volume = 382 | issue = 1 | pages = 521–6 | date = Jan 2014 | pmid = 24145129 | pmc = 3850748 | doi = 10.1016/j.mce.2013.10.008 }}</ref>
'''Osteocalcin''' is a noncollagenous protein found in bone and dentin.  It is secreted by [[osteoblasts]] and thought to play a role in mineralization and calcium ion homeostasis. It has been stipulated that osteocalcin may also function as a negative regulator of bone formation, although its exact role is unknown.


In August 2007, it was reported<ref>"[http://www.columbia.edu/cu/news/07/08/bones.html Research Shows Skeleton to be Endocrine Organ]" Columbia University News, August 09, 2007''</ref> that osteocalcin acts as a [[hormone]] in the body, causing [[beta cells]] in the [[pancreas]] to release more [[insulin]], and at the same time directing [[fat cells]] to release the hormone [[adiponectin]], which increases sensitivity to insulin.
Osteocalcin also acts on myocytes to promote energy availability and utilization and in this manner favors exercise capacity.<ref>{{cite journal | vauthors = Mera P, Laue K, Ferron M, Confavreux C, Wei J, Galán-Díez M, Lacampagne A, Mitchell SJ, Mattison JA, Chen Y, Bacchetta J, Szulc P, Kitsis RN, de Cabo R, Friedman RA, Torsitano C, McGraw TE, Puchowicz M, Kurland I, Karsenty G | display-authors = 6 | title = Osteocalcin Signaling in Myofibers Is Necessary and Sufficient for Optimum Adaptation to Exercise | journal = Cell Metabolism | volume = 23 | issue = 6 | pages = 1078–1092 | date = June 2016 | pmid = 27304508 | pmc = 4910629 | doi = 10.1016/j.cmet.2016.05.004 }}</ref>


==Use as a biochemical marker for bone formation==
== Use as a biochemical marker for bone formation ==
As osteocalcin is manufactured by osteoblasts, it is often used as a biochemical marker, or biomarker, for the bone formation process. It has been routinely observed that higher serum-osteocalcin levels are relatively well correlated with increases in bone mineral density (BMD) during treatment with anabolic bone formation drugs for osteoporosis, such as [[Teriparatide|Forteo]]. In many studies, Osteocalcin is used as a preliminary biomarker on the effectiveness of a given drug on bone formation.


==References==
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 (BMD) 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.<ref name="bone turnover">{{cite journal | vauthors = Bharadwaj S, Naidu AG, Betageri GV, Prasadarao NV, Naidu AS | title = Milk ribonuclease-enriched lactoferrin induces positive effects on bone turnover markers in postmenopausal women | journal = Osteoporosis International | volume = 20 | issue = 9 | pages = 1603–11 | date = Sep 2009 | pmid = 19172341 | doi = 10.1007/s00198-009-0839-8 }}</ref>


<div class="references-small">
== References ==
{{reflist|2}}
{{Reflist}}
</div>


==External links==
== Further reading ==
{{refbegin | 2}}
* {{cite journal | vauthors = Kamdem LK, Hamilton L, Cheng C, Liu W, Yang W, Johnson JA, Pui CH, Relling MV | title = Genetic predictors of glucocorticoid-induced hypertension in children with acute lymphoblastic leukemia | journal = Pharmacogenetics and Genomics | volume = 18 | issue = 6 | pages = 507–14 | date = Jun 2008 | pmid = 18496130 | doi = 10.1097/FPC.0b013e3282fc5801 }}
* {{cite journal | vauthors = Lin GT, Tseng HF, Chang CK, Chuang LY, Liu CS, Yang CH, Tu CJ, Wang EC, Tan HF, Chang CC, Wen CH, Chen HC, Chang HW | title = SNP combinations in chromosome-wide genes are associated with bone mineral density in Taiwanese women | journal = The Chinese Journal of Physiology | volume = 51 | issue = 1 | pages = 32–41 | date = Feb 2008 | pmid = 18551993 | doi =  }}
* {{cite journal | vauthors = Lumachi F, Camozzi V, Tombolan V, Luisetto G | title = Bone mineral density, osteocalcin, and bone-specific alkaline phosphatase in patients with insulin-dependent diabetes mellitus | journal = Annals of the New York Academy of Sciences | volume = 1173 Suppl 1 | issue =  | pages = E64-7 | date = Sep 2009 | pmid = 19751417 | doi = 10.1111/j.1749-6632.2009.04955.x }}
* {{cite journal | vauthors = Kanazawa I, Yamaguchi T, Yamamoto M, Yamauchi M, Yano S, Sugimoto T | title = Serum osteocalcin/bone-specific alkaline phosphatase ratio is a predictor for the presence of vertebral fractures in men with type 2 diabetes | journal = Calcified Tissue International | volume = 85 | issue = 3 | pages = 228–34 | date = Sep 2009 | pmid = 19641839 | doi = 10.1007/s00223-009-9272-4 }}
* {{cite journal | vauthors = Makita N, Suzuki M, Asami S, Takahata R, Kohzaki D, Kobayashi S, Hakamazuka T, Hozumi N | title = Two of four alternatively spliced isoforms of RUNX2 control osteocalcin gene expression in human osteoblast cells | journal = Gene | volume = 413 | issue = 1-2 | pages = 8–17 | date = Apr 2008 | pmid = 18321663 | doi = 10.1016/j.gene.2007.12.025 }}
* {{cite journal | vauthors = Desbois C, Karsenty G | title = Osteocalcin cluster: implications for functional studies | journal = Journal of Cellular Biochemistry | volume = 57 | issue = 3 | pages = 379–83 | date = Mar 1995 | pmid = 7768973 | doi = 10.1002/jcb.240570302 }}
* {{cite journal | vauthors = Salem AM, Zohny SF, Abd El-Wahab MM, Hamdy R | title = Predictive value of osteocalcin and beta-CrossLaps in metastatic breast cancer | journal = Clinical Biochemistry | volume = 40 | issue = 16-17 | pages = 1201–8 | date = Nov 2007 | pmid = 17889845 | doi = 10.1016/j.clinbiochem.2007.07.006 }}
* {{cite journal | vauthors = Im JA, Yu BP, Jeon JY, Kim SH | title = Relationship between osteocalcin and glucose metabolism in postmenopausal women | journal = Clinica Chimica Acta; International Journal of Clinical Chemistry | volume = 396 | issue = 1-2 | pages = 66–9 | date = Oct 2008 | pmid = 18657532 | doi = 10.1016/j.cca.2008.07.001 }}
* {{cite journal | vauthors = Ba Y, Huang H, Yang Y, Cui L, Zhu J, Zhu C, Liu J, Zhang Y | title = The association between osteocalcin gene polymorphism and dental fluorosis among children exposed to fluoride in People's Republic of China | journal = Ecotoxicology and Environmental Safety | volume = 72 | issue = 8 | pages = 2158–61 | date = Nov 2009 | pmid = 19767102 | doi = 10.1016/j.ecoenv.2009.08.014 }}
* {{cite journal | vauthors = Hwang YC, Jeong IK, Ahn KJ, Chung HY | title = The uncarboxylated form of osteocalcin is associated with improved glucose tolerance and enhanced beta-cell function in middle-aged male subjects | journal = Diabetes/Metabolism Research and Reviews | volume = 25 | issue = 8 | pages = 768–72 | date = Nov 2009 | pmid = 19877133 | doi = 10.1002/dmrr.1045 }}
* {{cite journal | vauthors = Yerges LM, Klei L, Cauley JA, Roeder K, Kammerer CM, Moffett SP, Ensrud KE, Nestlerode CS, Marshall LM, Hoffman AR, Lewis C, Lang TF, Barrett-Connor E, Ferrell RE, Orwoll ES, Zmuda JM | title = High-density association study of 383 candidate genes for volumetric BMD at the femoral neck and lumbar spine among older men | journal = Journal of Bone and Mineral Research | volume = 24 | issue = 12 | pages = 2039–49 | date = Dec 2009 | pmid = 19453261 | pmc = 2791518 | doi = 10.1359/jbmr.090524 }}
* {{cite journal | vauthors = Yu S, Jiang Y, Galson DL, Luo M, Lai Y, Lu Y, Ouyang HJ, Zhang J, Xiao G | title = General transcription factor IIA-gamma increases osteoblast-specific osteocalcin gene expression via activating transcription factor 4 and runt-related transcription factor 2 | journal = The Journal of Biological Chemistry | volume = 283 | issue = 9 | pages = 5542–53 | date = Feb 2008 | pmid = 18171674 | pmc = 2736298 | doi = 10.1074/jbc.M705653200 }}
* {{cite journal | vauthors = Kayed H, Bekasi S, Keleg S, Michalski CW, Giese T, Friess H, Kleeff J | title = BGLAP is expressed in pancreatic cancer cells and increases their growth and invasion | journal = Molecular Cancer | volume = 6 | issue =  | pages = 83 | year = 2007 | pmid = 18163903 | pmc = 2245975 | doi = 10.1186/1476-4598-6-83 }}
* {{cite journal | vauthors = French D, Hamilton LH, Mattano LA, Sather HN, Devidas M, Nachman JB, Relling MV | title = A PAI-1 (SERPINE1) polymorphism predicts osteonecrosis in children with acute lymphoblastic leukemia: a report from the Children's Oncology Group | journal = Blood | volume = 111 | issue = 9 | pages = 4496–9 | date = May 2008 | pmid = 18285546 | pmc = 2343589 | doi = 10.1182/blood-2007-11-123885 }}
* {{cite journal | vauthors = Pittas AG, Harris SS, Eliades M, Stark P, Dawson-Hughes B | title = Association between serum osteocalcin and markers of metabolic phenotype | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 94 | issue = 3 | pages = 827–32 | date = Mar 2009 | pmid = 19088165 | pmc = 2681283 | doi = 10.1210/jc.2008-1422 }}
* {{cite journal | vauthors = Kindblom JM, Ohlsson C, Ljunggren O, Karlsson MK, Tivesten A, Smith U, Mellström D | title = Plasma osteocalcin is inversely related to fat mass and plasma glucose in elderly Swedish men | journal = Journal of Bone and Mineral Research | volume = 24 | issue = 5 | pages = 785–91 | date = May 2009 | pmid = 19063687 | doi = 10.1359/jbmr.081234 }}
* {{cite journal | vauthors = Wahlgren CM, Zheng W, Shaalan W, Tang J, Bassiouny HS | title = Human carotid plaque calcification and vulnerability. Relationship between degree of plaque calcification, fibrous cap inflammatory gene expression and symptomatology | journal = Cerebrovascular Diseases | volume = 27 | issue = 2 | pages = 193–200 | year = 2009 | pmid = 19136823 | doi = 10.1159/000189204 }}
* {{cite journal | vauthors = Lumachi F, Ermani M, Camozzi V, Tombolan V, Luisetto G | title = Changes of bone formation markers osteocalcin and bone-specific alkaline phosphatase in postmenopausal women with osteoporosis | journal = Annals of the New York Academy of Sciences | volume = 1173 Suppl 1 | issue =  | pages = E60-3 | date = Sep 2009 | pmid = 19751416 | doi = 10.1111/j.1749-6632.2009.04953.x }}
* {{cite journal | vauthors = Born AK, Rottmar M, Lischer S, Pleskova M, Bruinink A, Maniura-Weber K | title = Correlating cell architecture with osteogenesis: first steps towards live single cell monitoring | journal = European Cells & Materials | volume = 18 | issue =  | pages = 49–60, 61–2; discussion 60 | year = 2009 | pmid = 19856264 | doi =  }}
* {{cite journal | vauthors = Fujisawa R | title = [Recent advances in research on bone matrix proteins] | journal = Nihon Rinsho. Japanese Journal of Clinical Medicine | volume = 60 Suppl 3 | issue =  | pages = 72–8 | date = Mar 2002 | pmid = 11979972 | doi =  }}
{{refend}}
 
== External links ==
* {{MeshName|Osteocalcin}}
* {{MeshName|Osteocalcin}}


{{PDB Gallery|geneid=632}}
{{Calcium-binding proteins}}
{{Calcium-binding proteins}}
{{hormones}}
{{hormones}}


[[Category:Proteins]]
[[Category:Peptide hormones]]
[[Category:Endocrinology]]
[[Category:Hormones of bone]]
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{{WikiDoc Sources}}
 
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[[ja:オステオカルシン]]

Latest revision as of 08:58, 5 November 2018

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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UniProt

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RefSeq (mRNA)

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RefSeq (protein)

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Not to be confused with Osteonectin or Osteopontin.

Osteocalcin, also known as bone gamma-carboxyglutamic acid-containing protein (BGLAP), is a noncollagenous protein hormone found in bone and dentin. Because it has gla domains, its synthesis is vitamin K dependent. In humans, the osteocalcin is encoded by the BGLAP gene.[1][2] Its receptor is GPRC6A.[3]

Function

Osteocalcin is secreted solely by osteoblasts and thought to play a role in the body's metabolic regulation and is pro-osteoblastic, or bone-building, by nature.[4] It is also implicated in bone mineralization and calcium ion homeostasis. Osteocalcin acts as a hormone in the body, causing beta cells in the pancreas to release more insulin, and at the same time directing fat cells to release the hormone adiponectin, which increases sensitivity to insulin.[4]

Osteocalcin acts on Leydig cells of the testis to stimulate testosterone biosynthesis and therefore affect male fertility.[5]

Osteocalcin also acts on myocytes to promote energy availability and utilization and in this manner favors exercise capacity.[6]

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 (BMD) 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.[7]

References

  1. ↑ Puchacz E, Lian JB, Stein GS, Wozney J, Huebner K, Croce C (May 1989). "Chromosomal localization of the human osteocalcin gene". Endocrinology. 124 (5): 2648–50. doi:10.1210/endo-124-5-2648. PMID 2785029.
  2. ↑ Cancela L, Hsieh CL, Francke U, Price PA (Sep 1990). "Molecular structure, chromosome assignment, and promoter organization of the human matrix Gla protein gene". The Journal of Biological Chemistry. 265 (25): 15040–8. PMID 2394711.
  3. ↑ Pi M, Wu Y, Quarles LD (Jul 2011). "GPRC6A mediates responses to osteocalcin in β-cells in vitro and pancreas in vivo". Journal of Bone and Mineral Research. 26 (7): 1680–1683. doi:10.1002/jbmr.390. PMC 5079536. PMID 21425331.
  4. ↑ 4.0 4.1 Lee NK, Sowa H, Hinoi E, Ferron M, Ahn JD, Confavreux C, Dacquin R, Mee PJ, McKee MD, Jung DY, Zhang Z, Kim JK, Mauvais-Jarvis F, Ducy P, Karsenty G (Aug 2007). "Endocrine regulation of energy metabolism by the skeleton". Cell. 130 (3): 456–69. doi:10.1016/j.cell.2007.05.047. PMC 2013746. PMID 17693256.
  5. ↑ Karsenty G, Oury F (Jan 2014). "Regulation of male fertility by the bone-derived hormone osteocalcin". Molecular and Cellular Endocrinology. 382 (1): 521–6. doi:10.1016/j.mce.2013.10.008. PMC 3850748. PMID 24145129.
  6. ↑ Mera P, Laue K, Ferron M, Confavreux C, Wei J, Galán-Díez M, et al. (June 2016). "Osteocalcin Signaling in Myofibers Is Necessary and Sufficient for Optimum Adaptation to Exercise". Cell Metabolism. 23 (6): 1078–1092. doi:10.1016/j.cmet.2016.05.004. PMC 4910629. PMID 27304508.
  7. ↑ Bharadwaj S, Naidu AG, Betageri GV, Prasadarao NV, Naidu AS (Sep 2009). "Milk ribonuclease-enriched lactoferrin induces positive effects on bone turnover markers in postmenopausal women". Osteoporosis International. 20 (9): 1603–11. doi:10.1007/s00198-009-0839-8. PMID 19172341.

Further reading

External links

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