Biology:Osteocalcin

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Short description: Mammalian protein found in Homo sapiens


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example


Osteocalcin, also known as bone gamma-carboxyglutamic acid-containing protein (BGLAP), is a small (49-amino-acid[1]) noncollagenous protein hormone found in bone and dentin, first identified as a calcium-binding protein.[2]

Because osteocalcin has gla domains, its synthesis is vitamin K dependent. In humans, osteocalcin is encoded by the BGLAP gene.[3][4] Its receptors include GPRC6A, GPR158, and possibly a third, yet-to-be-identified receptor.[5][6] There is evidence that GPR37 might be the third osteocalcin receptor.[7]

Function

Osteocalcin is secreted solely by osteoblasts and thought to play a role in the body's metabolic regulation.[8] 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.[9]

  • In the pancreas, osteocalcin acts on beta cells, causing beta cells in the pancreas to release more insulin.[8]
  • In fat cells, osteocalcin triggers the release of the hormone adiponectin, which increases sensitivity to insulin.[8]
  • In muscle, osteocalcin acts on myocytes to promote energy availability and utilization and in this manner favors exercise capacity.[10][11]
  • In the testes, osteocalcin acts on Leydig cells, stimulating testosterone biosynthesis and therefore affects male fertility.[12]
  • In the brain, osteocalcin plays an important role in development and functioning including spatial learning and memory.[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.[14]

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.[15]

References

  1. ↑ Hauschka, P. V.; Carr, S. A.; Biemann, K. (1982). "Primary structure of monkey osteocalcin". Biochemistry 21 (4): 638–42. doi:10.1021/bi00533a006. PMID 6978733. 
  2. ↑ "Timed appearance of a calcium-binding protein containing gamma-carboxyglutamic acid in developing chick bone". Developmental Biology 65 (2): 426–34. August 1978. doi:10.1016/0012-1606(78)90038-6. PMID 680371. 
  3. ↑ "Chromosomal localization of the human osteocalcin gene". Endocrinology 124 (5): 2648–50. May 1989. doi:10.1210/endo-124-5-2648. PMID 2785029. 
  4. ↑ "Molecular structure, chromosome assignment, and promoter organization of the human matrix Gla protein gene". The Journal of Biological Chemistry 265 (25): 15040–8. September 1990. doi:10.1016/S0021-9258(18)77221-9. PMID 2394711. 
  5. ↑ "GPRC6A mediates responses to osteocalcin in β-cells in vitro and pancreas in vivo". Journal of Bone and Mineral Research 26 (7): 1680–3. July 2011. doi:10.1002/jbmr.390. PMID 21425331. 
  6. ↑ "Mediation of the Acute Stress Response by the Skeleton". Cell Metabolism 30 (5): 890–902.e8. September 2019. doi:10.1016/j.cmet.2019.08.012. PMID 31523009. 
  7. ↑ "Osteocalcin attenuates oligodendrocyte differentiation and myelination via GPR37 signaling in the mouse brain". Science Advances 7 (43): eabi5811. October 2021. doi:10.1126/sciadv.abi5811. PMID 34678058. Bibcode: 2021SciA....7.5811Q. 
  8. ↑ 8.0 8.1 8.2 "Endocrine regulation of energy metabolism by the skeleton". Cell 130 (3): 456–69. August 2007. doi:10.1016/j.cell.2007.05.047. PMID 17693256. 
  9. ↑ "Bone and Muscle Endocrine Functions: Unexpected Paradigms of Inter-organ Communication". Cell 164 (6): 1248–1256. March 2016. doi:10.1016/j.cell.2016.02.043. PMID 26967290. 
  10. ↑ "Osteocalcin Signaling in Myofibers Is Necessary and Sufficient for Optimum Adaptation to Exercise". Cell Metabolism 23 (6): 1078–1092. June 2016. doi:10.1016/j.cmet.2016.05.004. PMID 27304508. 
  11. ↑ Dance, Amber (23 February 2022). "Fun facts about bones: More than just scaffolding". Knowable Magazine. doi:10.1146/knowable-022222-1. https://knowablemagazine.org/article/health-disease/2022/fun-facts-about-bones-more-just-scaffolding. Retrieved 8 March 2022. 
  12. ↑ "Regulation of male fertility by the bone-derived hormone osteocalcin". Molecular and Cellular Endocrinology 382 (1): 521–526. January 2014. doi:10.1016/j.mce.2013.10.008. PMID 24145129. 
  13. ↑ "Osteocalcin in the brain: from embryonic development to age-related decline in cognition". Nature Reviews. Endocrinology 14 (3): 174–182. March 2018. doi:10.1038/nrendo.2017.181. PMID 29376523. 
  14. ↑ "Mediation of the Acute Stress Response by the Skeleton". Cell Metabolism 30 (5): 890–902.e8. 2019. doi:10.1016/j.cmet.2019.08.012. PMID 31523009. 
  15. ↑ "Milk ribonuclease-enriched lactoferrin induces positive effects on bone turnover markers in postmenopausal women". Osteoporosis International 20 (9): 1603–11. September 2009. doi:10.1007/s00198-009-0839-8. PMID 19172341. 

Further reading

External links



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