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
AliasiBGLAP
Vanjski ID-jeviOMIM: 112260 MGI: 88155 HomoloGene: 104130 GeneCards: BGLAP
Lokacija gena (čovjek)
Hromosom 1 (čovjek)
Hrom.Hromosom 1 (čovjek)[1]
Hromosom 1 (čovjek)
Genomska lokacija za BGLAP
Genomska lokacija za BGLAP
Bend1q22Početak156,242,184 bp[1]
Kraj156,243,317 bp[1]
Lokacija gena (miš)
Hromosom 3 (miš)
Hrom.Hromosom 3 (miš)[2]
Hromosom 3 (miš)
Genomska lokacija za BGLAP
Genomska lokacija za BGLAP
Bend3 F1|3 38.81 cMPočetak88,275,923 bp[2]
Kraj88,280,050 bp[2]
Ontologija gena
Molekularna funkcija calcium ion binding
structural molecule activity
metal ion binding
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
VrsteČovjekMiš
Entrez
Ensembl
UniProt
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 MbChr 3: 88.28 – 88.28 Mb
PubMed pretraga[3][4]
Wikipodaci
Pogledaj/uredi – čovjekPogledaj/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 uredi

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]

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 uredi

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 uredi

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000242252 - Ensembl, maj 2017
  2. ^ a b c 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. ^ a b c 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 uredi

Vanjski linkovi uredi