Osteokalcin

Osteokalcin – poznat i kao kostni protein sa gama-karboksiglutaminskom kiselinom (BGLAP) − je mali, 49-aminokiselinski^[5] nekolageni proteinski hormon, pronađen u kostima i dentinu, prvi put identificiran kao protein koji veže kalcij u kokošjoj kosti.^[6]

BGLAP
Identifikatori
Aliasi	BGLAP
Vanjski ID-jevi	OMIM: 112260 MGI: 88155 HomoloGene: 104130 GeneCards: BGLAP
Lokacija gena (čovjek) Hrom. Hromosom 1 (čovjek)[1] Bend 1q22 Početak 156,242,184 bp[1] Kraj 156,243,317 bp[1]
Lokacija gena (miš) Hrom. Hromosom 3 (miš)[2] Bend 3 F1|3 38.81 cM Početak 88,275,923 bp[2] Kraj 88,280,050 bp[2]
Ontologija gena Molekularna funkcija • calcium ion binding • structural molecule activity • vezivanje iona metala • hydroxyapatite binding • structural constituent of bone Ćelijska komponenta • citoplazma • perikaryon • rough endoplasmic reticulum • Golđijev aparat • projekcija ćelije • endoplasmic reticulum lumen • extracellular region • dendrit • Golgi lumen • Vanćelijsko • Vezikula Biološki proces • skeletal system development • bone mineralization • response to vitamin D • GO:1904578 response to organic cyclic compound • ossification • response to testosterone • regulation of bone mineralization • biomineral tissue development • cellular response to growth factor stimulus • response to mechanical stimulus • GO:0010260 Starenje • response to zinc ion • response to glucocorticoid • cellular response to vitamin D • response to activity • response to estrogen • odontogenesis • endoplasmic reticulum to Golgi vesicle-mediated transport • response to gravity • response to vitamin K • response to hydroxyisoflavone • Ćelijska adhezija • response to nutrient levels • regulation of osteoclast differentiation • osteoblast differentiation • response to inorganic substance • osteoblast development • response to ethanol • regulation of bone resorption • bone development • regulation of cellular response to insulin stimulus Izvori:Amigo / QuickGO
Ortolozi
Vrste	Čovjek	Miš
Entrez	632	12095
Ensembl	ENSG00000242252	ENSMUSG00000074489
UniProt	P02818	P54615
RefSeq (mRNK)	NM_199173	NM_031368 NM_001305448 NM_001305449 NM_001305450
RefSeq (bjelančevina)	NP_954642	NP_001292377 NP_001292378 NP_001292379 NP_112736
Lokacija (UCSC)	Chr 1: 156.24 – 156.24 Mb	Chr 3: 88.28 – 88.28 Mb
PubMed pretraga	[3]	[4]
Wikipodaci
Pogledaj/uredi – čovjek Pogledaj/uredi – miš

Budući da osteokalcin ima gla-domen, njegova sinteza zavisi od vitamina K. Kod ljudi, osteokalcin kodira gen BGLA.^[7][8] Njegovi receptori uključuju GPRC6A, GPR158 i, možda, treći receptor koji tek treba identificirati.^[9][10]

Funkcija

Osteokalcin luče isključivo osteoblasti i smatra se da u tijelu ima ulogu regulatora metabolizma.^[11] U svom karboksiliranom obliku direktno veže kalcij i tako se koncentrira u kostima.

U svom karboksiliranom obliku osteokalcin djeluje kao hormon u tijelu, signalizirajući u gušterači, mastima, mišićima, sjemenicima i mozgu.^[12]

• U gušterači, osteokalcin djeluje na beta-ćelije, uzrokujući da one u gušterači oslobađaju više insulina.^[11]
• U masnim ćelijama, osteokalcin pokreće oslobađanje hormona adiponektina, što povećava osetljivost na insulin.^[11]
• U mišićima djeluje na miocite, promovirajući dostupnost i korištenje energije i na taj način favorizira sposobnost vježbanja i drugih fizičkih napora.^[13]
• U sjemenicima djeluje na Leydigove ćelije, stimulirajući biosintezu testosterona i stoga utiče na plodnost muškaraca.^[14]
• U mozgu, osteokalcin ima važnu ulogu u njegovom razvoju i funkcioniranju.^[15]

Akutni odgovor na stres, kolokvijalno poznat kao reakcija borba ili bijeg, stimulira oslobađanje osteokalcina iz kostiju: za nekoliko minuta kod miševa, pacova i ljudi. Injekcije sa visokom razinom osteokalcina same mogu pokrenuti ASR u slučaju nadbubrežne insuficijencije.^[16]

Upotreba kao biohemijskog markera formiranosti kosti

Kako osteoblasti proizvode osteokalcin, on se često koristi kao marker za proces formiranja kostiju. Primijećeno je da su više razine osteokalcina u serumu relativno dobro povezani sa porastom mineralne gustine kosti, tokom liječenja anaboličkim lijekovima za stvaranje kostiju u slučaju osteoporoze, kao što je teriparatid. U mnogim studijama osteokalcin se koristi kao preliminarni biomarker efikasnosti datog lijeka na stvaranje kostiju. Naprimjer, jedno istraživanje, koje je imalo za cilj proučavanje efikasnosti glikoproteina zvanog laktoferin na stvaranje kostiju, koristilo je osteokalcin kao mjeru aktivnosti osteoblasta.^[17]

Reference

1. GRCh38: Ensembl release 89: ENSG00000242252 - Ensembl, maj 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000074489 - Ensembl, maj 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. 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.
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.
7. Puchacz E, Lian JB, Stein GS, Wozney J, Huebner K, Croce C (maj 1989). "Chromosomal localization of the human osteocalcin gene". Endocrinology. 124 (5): 2648–50. doi:10.1210/endo-124-5-2648. PMID 2785029.
8. Cancela L, Hsieh CL, Francke U, Price PA (septembar 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.
9. Pi M, Wu Y, Quarles LD (juli 2011). "GPRC6A mediates responses to osteocalcin in β-cells in vitro and pancreas in vivo". Journal of Bone and Mineral Research. 26 (7): 1680–3. doi:10.1002/jbmr.390. PMC 5079536. PMID 21425331.
10. Berger JM, Singh P, Khrimian L, Morgan DA, Chowdhury S, Arteaga-Solis E, et al. (septembar 2019). "Mediation of the Acute Stress Response by the Skeleton". Cell Metabolism. 30 (5): 890–902.e8. doi:10.1016/j.cmet.2019.08.012. PMC 6834912. PMID 31523009.
11. Lee NK, Sowa H, Hinoi E, Ferron M, Ahn JD, Confavreux C, et al. (august 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.
12. Karsenty G, Olson EN (mart 2016). "Bone and Muscle Endocrine Functions: Unexpected Paradigms of Inter-organ Communication". Cell. 164 (6): 1248–1256. doi:10.1016/j.cell.2016.02.043. PMC 4797632. PMID 26967290.
13. Mera P, Laue K, Ferron M, Confavreux C, Wei J, Galán-Díez M, et al. (juni 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.
14. Karsenty G, Oury F (januar 2014). "Regulation of male fertility by the bone-derived hormone osteocalcin". Molecular and Cellular Endocrinology. 382 (1): 521–526. doi:10.1016/j.mce.2013.10.008. PMC 3850748. PMID 24145129.
15. Obri A, Khrimian L, Karsenty G, Oury F (mart 2018). "Osteocalcin in the brain: from embryonic development to age-related decline in cognition". Nature Reviews. Endocrinology. 14 (3): 174–182. doi:10.1038/nrendo.2017.181. PMC 5958904. PMID 29376523.
16. Meyer-Berger J, Singh P, Khrimian L, Morgan D, Chowdhury S, Arteaga-Solis E, Horvath T, Domingos A, Marsland A, Yadav V, Rahmouni K, Gao X, Karsenty G (2019). "Mediation of the Acute Stress Response by the Skeleton". Cell Metabolism. 30 (5): 890–902.e8. doi:10.1016/j.cmet.2019.08.012. PMC 6834912. PMID 31523009.
17. Bharadwaj S, Naidu AG, Betageri GV, Prasadarao NV, Naidu AS (septembar 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.

Dopunska literatura

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• Lumachi F, Camozzi V, Tombolan V, Luisetto G (septembar 2009). "Bone mineral density, osteocalcin, and bone-specific alkaline phosphatase in patients with insulin-dependent diabetes mellitus". Annals of the New York Academy of Sciences. 1173 Suppl 1: E64-7. doi:10.1111/j.1749-6632.2009.04955.x. PMID 19751417.
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• Makita N, Suzuki M, Asami S, Takahata R, Kohzaki D, Kobayashi S, et al. (april 2008). "Two of four alternatively spliced isoforms of RUNX2 control osteocalcin gene expression in human osteoblast cells". Gene. 413 (1–2): 8–17. doi:10.1016/j.gene.2007.12.025. PMID 18321663.
• Desbois C, Karsenty G (mart 1995). "Osteocalcin cluster: implications for functional studies". Journal of Cellular Biochemistry. 57 (3): 379–83. doi:10.1002/jcb.240570302. PMID 7768973.
• Salem AM, Zohny SF, Abd El-Wahab MM, Hamdy R (novembar 2007). "Predictive value of osteocalcin and beta-CrossLaps in metastatic breast cancer". Clinical Biochemistry. 40 (16–17): 1201–8. doi:10.1016/j.clinbiochem.2007.07.006. PMID 17889845.
• Im JA, Yu BP, Jeon JY, Kim SH (oktobar 2008). "Relationship between osteocalcin and glucose metabolism in postmenopausal women". Clinica Chimica Acta; International Journal of Clinical Chemistry. 396 (1–2): 66–9. doi:10.1016/j.cca.2008.07.001. PMID 18657532.
• Ba Y, Huang H, Yang Y, Cui L, Zhu J, Zhu C, et al. (novembar 2009). "The association between osteocalcin gene polymorphism and dental fluorosis among children exposed to fluoride in People's Republic of China". Ecotoxicology and Environmental Safety. 72 (8): 2158–61. doi:10.1016/j.ecoenv.2009.08.014. PMID 19767102.
• Hwang YC, Jeong IK, Ahn KJ, Chung HY (novembar 2009). "The uncarboxylated form of osteocalcin is associated with improved glucose tolerance and enhanced beta-cell function in middle-aged male subjects". Diabetes/Metabolism Research and Reviews. 25 (8): 768–72. doi:10.1002/dmrr.1045. PMID 19877133.
• Yerges LM, Klei L, Cauley JA, Roeder K, Kammerer CM, Moffett SP, et al. (decembar 2009). "High-density association study of 383 candidate genes for volumetric BMD at the femoral neck and lumbar spine among older men". Journal of Bone and Mineral Research. 24 (12): 2039–49. doi:10.1359/jbmr.090524. PMC 2791518. PMID 19453261.
• Yu S, Jiang Y, Galson DL, Luo M, Lai Y, Lu Y, et al. (februar 2008). "General transcription factor IIA-gamma increases osteoblast-specific osteocalcin gene expression via activating transcription factor 4 and runt-related transcription factor 2". The Journal of Biological Chemistry. 283 (9): 5542–53. doi:10.1074/jbc.M705653200. PMC 2736298. PMID 18171674.
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Vanjski linkovi

• Osteocalcin na US National Library of Medicine Medical Subject Headings (MeSH)