View source for Osteocalcin

{{Infobox_gene}}
{{Distinguish|Osteonectin|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 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>

== 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>

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 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 ==

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>

== References ==
{{Reflist}}

== 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}}

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

[[Category:Peptide hormones]]
[[Category:Hormones of bone]]