骨鈣蛋白

Bone gamma-carboxyglutamate (gla) protein
骨含伽馬羧酸蛋白
Bone gamma-carboxyglutamate (gla) protein; 骨含伽馬羧酸蛋白
	PDB rendering based on 1q8h.
有效結構
PDB	直系同源檢索：PDBe, RCSB
PDB查詢代碼列表
	1q3m, 1q8h
標識
代號	BGLAP; BGP; OC; OCN
擴展標識	遺傳學：112260 鼠基因：88156 同源基因：104130 GeneCards: BGLAP Gene
基因本體論描述
分子功能	· structural molecule activity; · calcium ion binding; · structural constituent of bone; · hydroxyapatite binding;
細胞成分	· extracellular region; · extracellular space; · rough endoplasmic reticulum; · Golgi apparatus; · dendrite; · membrane-bounded vesicle; · perikaryon;
生物過程	· skeletal system development; · osteoblast differentiation; · osteoblast development; · cell adhesion; · cell aging; · response to mechanical stimulus; · response to gravity; · response to zinc ion; · response to activity; · bone mineralization; · regulation of bone mineralization; · response to vitamin K; · response to vitamin D; · response to testosterone stimulus; · response to hydroxyisoflavone; · odontogenesis; · response to drug; · response to estrogen stimulus; · regulation of bone resorption; · response to ethanol; · regulation of osteoclast differentiation; · response to glucocorticoid stimulus; · bone development; · cellular response to vitamin D; · cellular response to growth factor stimulus;
	Sources: Amigo / QuickGO
直系同源體
物種	人類
Entrez	632
Ensembl	ENSG00000242252
UniProt	P02818
mRNA序列	NM_199173
蛋白序列	NP_954642
基因位置	Chr 1:; 156.21 – 156.21 Mb
PubMed查詢	[1]
	閱; 論; 編;

骨鈣蛋白，也被稱為骨含伽馬羧酸蛋白 (BGLAP)，是一種非膠原蛋白質，可見於骨或牙本質之中。因其含伽馬羧酸基團, 所以其合成是維生素K依賴性的。在人體，骨鈣蛋白是由BGLAP 基因編碼的。^[1]^[2] 其受體是 GPRC6A.^[3]

功能

骨鈣蛋白僅由成骨細胞分泌，它在人體代謝調節方面有一定作用，並具有「促成骨」作用。^[4] 它也涉及骨礦化和鈣離子動態平衡。骨鈣蛋白在人體內也是一種荷爾蒙，它可促使胰腺的beta細胞釋放更多的胰島素, 並同時指示脂肪細胞釋放荷爾蒙脂聯素來提高對胰島素的敏感性。^[4]

當前的數據暗示骨鈣蛋白在男性生育能力方面扮演的一種可能的角色。^[5] 來自哥倫比亞大學醫學中心的研究提出骨鈣蛋白可能增強睪酮的分泌。^[6] 雖然這些研究只由單獨的一家實驗室進行，但至少有其它兩個團體曾獨立確認了骨鈣蛋白在胰島素分泌方面的作用。^[7]^[8]

用做成骨過程的生化標記

由於骨鈣蛋白是由成骨細胞產生，所以它常常被用作成骨過程標記。在使用針對成骨細胞的成骨促進藥物，如特立帕肽(Teriparatide)的治療過程當中，曾觀察到較高的血漿骨鈣蛋白水平與骨礦物質密度（BMD）之間有較高的相關性。在許多研究當中，骨鈣蛋白被用作一種指示某種藥物骨形成效應的基本的生化標記。例如，一項針對一種叫做乳鐵蛋白(lactoferrin)的糖蛋白對成骨過程效用的研究就使用了骨鈣蛋白作為成骨細胞活躍度的度量指標。^[9]

引用

^ Puchacz E, Lian JB, Stein GS, Wozney J, Huebner K, Croce C. 人类骨钙蛋白基因染色体定位. Endocrinology. May 1989, 124 (5): 2648–50. PMID 2785029. doi:10.1210/endo-124-5-2648.
^ Cancela L, Hsieh CL, Francke U, Price PA. 分子结构，染色体分配，以及人类基质Gla的蛋白质基因的启动子的组织. J. Biol. Chem. 1990，九月, 265 (25): 15040–8. PMID 2394711. 請檢查|date=中的日期值 (幫助)
^ 存档副本. [2014-10-18]. （原始內容存檔於2014-10-18）.
^ ^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. 骨骼对能量代谢的内分泌调节（Endocrine regulation of energy metabolism by the skeleton）. Cell. August 2007, 130 (3): 456–69. PMC 2013746  . PMID 17693256. doi:10.1016/j.cell.2007.05.047.
^ Franck Oury, Grzegorz Sumara, Olga Sumara, Mathieu Ferron, Haixin Chang, Charles E. Smith, Louis Hermo, Susan Suarez, Bryan L. Roth, Patricia Ducy et al.骨骼對男性生育力的內分泌調節（Endocrine Regulation of Male Fertility by the Skeleton）. Cell, 17 February 2011 doi:10.1016/j.cell.2011.02.004
^ 睪酮
^ Pi M, Wu Y, Quarles DL. GPRC6A介导体外beta细胞和体内胰腺对骨钙蛋白的反应（GPRC6A mediates responses to osteocalcin in beta-cells in vitro and pancreas in vivo）. JBMR. July 2011, 26 (7): 1680–1683. PMID 21425331. doi:10.1002/jbmr.390.
^ Fulzele K, Riddle RC, DiGirolamo DJ, Cao X, Wan C, Chen D, Faugere MC, Aja S, Hussain MA, Brüning JC, Clemens TL. Insulin receptor signaling in osteoblasts regulates postnatal bone acquisition and body composition. Cell. July 2010, 142 (2): 309–19. PMC 2925155  . PMID 20655471. doi:10.1016/j.cell.2010.06.002.
^ Bharadwaj S, Naidu AG, Betageri GV, Prasadarao NV, Naidu AS. Milk ribonuclease-enriched lactoferrin induces positive effects on bone turnover markers in postmenopausal women. Osteoporos Int. September 2009, 20 (9): 1603–11. PMID 19172341. doi:10.1007/s00198-009-0839-8.

延伸閱讀

Kamdem LK, Hamilton L, Cheng C; et al. Genetic predictors of glucocorticoid-induced hypertension in children with acute lymphoblastic leukemia.. Pharmacogenet. Genomics. 2008, 18 (6): 507–14. PMID 18496130. doi:10.1097/FPC.0b013e3282fc5801.
Lin GT, Tseng HF, Chang CK; et al. SNP combinations in chromosome-wide genes are associated with bone mineral density in Taiwanese women.. Chin J Physiol. 2008, 51 (1): 32–41. PMID 18551993.
Lumachi F, Camozzi V, Tombolan V, Luisetto G. Bone mineral density, osteocalcin, and bone-specific alkaline phosphatase in patients with insulin-dependent diabetes mellitus.. Annals of the New York Academy of Sciences. 2009,. 1173 Suppl 1: E64–7. PMID 19751417. doi:10.1111/j.1749-6632.2009.04955.x.
Kanazawa I, Yamaguchi T, Yamamoto M; et al. Serum osteocalcin/bone-specific alkaline phosphatase ratio is a predictor for the presence of vertebral fractures in men with type 2 diabetes.. Calcif. Tissue Int. 2009, 85 (3): 228–34. PMID 19641839. doi:10.1007/s00223-009-9272-4.
Makita N, Suzuki M, Asami S; et al. Two of four alternatively spliced isoforms of RUNX2 control osteocalcin gene expression in human osteoblast cells.. Gene. 2008, 413 (1-2): 8–17. PMID 18321663. doi:10.1016/j.gene.2007.12.025.
Desbois C, Karsenty G. Osteocalcin cluster: implications for functional studies.. J. Cell. Biochem. 1995, 57 (3): 379–83. PMID 7768973. doi:10.1002/jcb.240570302.
Salem AM, Zohny SF, Abd El-Wahab MM, Hamdy R. Predictive value of osteocalcin and beta-CrossLaps in metastatic breast cancer.. Clin. Biochem. 2007, 40 (16-17): 1201–8. PMID 17889845. doi:10.1016/j.clinbiochem.2007.07.006.
Im JA, Yu BP, Jeon JY, Kim SH. Relationship between osteocalcin and glucose metabolism in postmenopausal women.. Clin. Chim. Acta. 2008, 396 (1-2): 66–9. PMID 18657532. doi:10.1016/j.cca.2008.07.001.
Ba Y, Huang H, Yang Y; et al. The association between osteocalcin gene polymorphism and dental fluorosis among children exposed to fluoride in People's Republic of China.. Ecotoxicol. Environ. Saf. 2009, 72 (8): 2158–61. PMID 19767102. doi:10.1016/j.ecoenv.2009.08.014.
Hwang YC, Jeong IK, Ahn KJ, Chung HY. The uncarboxylated form of osteocalcin is associated with improved glucose tolerance and enhanced beta-cell function in middle-aged male subjects.. Diabetes Metab. Res. Rev. 2009, 25 (8): 768–72. PMID 19877133. doi:10.1002/dmrr.1045.
Yerges LM, Klei L, Cauley JA; et al. High-density association study of 383 candidate genes for volumetric BMD at the femoral neck and lumbar spine among older men.. J. Bone Miner. Res. 2009, 24 (12): 2039–49. PMC 2791518  . PMID 19453261. doi:10.1359/jbmr.090524.
Yu S, Jiang Y, Galson DL; et al. General transcription factor IIA-gamma increases osteoblast-specific osteocalcin gene expression via activating transcription factor 4 and runt-related transcription factor 2.. J. Biol. Chem. 2008, 283 (9): 5542–53. PMC 2736298  . PMID 18171674. doi:10.1074/jbc.M705653200.
Kayed H, Bekasi S, Keleg S; et al. BGLAP is expressed in pancreatic cancer cells and increases their growth and invasion.. Mol. Cancer. 2007, 6: 83. PMC 2245975  . PMID 18163903. doi:10.1186/1476-4598-6-83.
French D, Hamilton LH, Mattano LA; et al. A PAI-1 (SERPINE1) polymorphism predicts osteonecrosis in children with acute lymphoblastic leukemia: a report from the Children's Oncology Group.. Blood. 2008, 111 (9): 4496–9. PMC 2343589  . PMID 18285546. doi:10.1182/blood-2007-11-123885.
Pittas AG, Harris SS, Eliades M; et al. Association between serum osteocalcin and markers of metabolic phenotype.. J. Clin. Endocrinol. Metab. 2009, 94 (3): 827–32. PMC 2681283  . PMID 19088165. doi:10.1210/jc.2008-1422.
Kindblom JM, Ohlsson C, Ljunggren O; et al. Plasma osteocalcin is inversely related to fat mass and plasma glucose in elderly Swedish men.. J. Bone Miner. Res. 2009, 24 (5): 785–91. PMID 19063687. doi:10.1359/jbmr.081234.
Wahlgren CM, Zheng W, Shaalan W; et al. Human carotid plaque calcification and vulnerability. Relationship between degree of plaque calcification, fibrous cap inflammatory gene expression and symptomatology.. Cerebrovasc. Dis. 2009, 27 (2): 193–200. PMID 19136823. doi:10.1159/000189204.
Lumachi F, Ermani M, Camozzi V; et al. Changes of bone formation markers osteocalcin and bone-specific alkaline phosphatase in postmenopausal women with osteoporosis.. Annals of the New York Academy of Sciences. 2009,. 1173 Suppl 1: E60–3. PMID 19751416. doi:10.1111/j.1749-6632.2009.04953.x.
Born AK, Rottmar M, Lischer S; et al. Correlating cell architecture with osteogenesis: first steps towards live single cell monitoring.. Eur Cell Mater. 2009, 18: 49–60, 61–2; discussion 60. PMID 19856264.
Fujisawa R. [Recent advances in research on bone matrix proteins]. Nippon Rinsho. 2002,. 60 Suppl 3: 72–8. PMID 11979972.

外部連結

醫學主題詞表（MeSH）：Osteocalcin

[pmid2785029-1] Puchacz E, Lian JB, Stein GS, Wozney J, Huebner K, Croce C. 人类骨钙蛋白基因染色体定位. Endocrinology. May 1989, 124 (5): 2648–50. PMID 2785029. doi:10.1210/endo-124-5-2648.

[pmid2394711-2] Cancela L, Hsieh CL, Francke U, Price PA. 分子结构，染色体分配，以及人类基质Gla的蛋白质基因的启动子的组织. J. Biol. Chem. 1990，九月, 265 (25): 15040–8. PMID 2394711. 請檢查|date=中的日期值 (幫助)

[3] 存档副本. [2014-10-18]. （原始內容存檔於2014-10-18）.

[Lee_2007-4] 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. 骨骼对能量代谢的内分泌调节（Endocrine regulation of energy metabolism by the skeleton）. Cell. August 2007, 130 (3): 456–69. PMC 2013746  . PMID 17693256. doi:10.1016/j.cell.2007.05.047.

[5] Franck Oury, Grzegorz Sumara, Olga Sumara, Mathieu Ferron, Haixin Chang, Charles E. Smith, Louis Hermo, Susan Suarez, Bryan L. Roth, Patricia Ducy et al.骨骼對男性生育力的內分泌調節（Endocrine Regulation of Male Fertility by the Skeleton）. Cell, 17 February 2011 doi:10.1016/j.cell.2011.02.004

[6] 睪酮

[Pi_2011-7] Pi M, Wu Y, Quarles DL. GPRC6A介导体外beta细胞和体内胰腺对骨钙蛋白的反应（GPRC6A mediates responses to osteocalcin in beta-cells in vitro and pancreas in vivo）. JBMR. July 2011, 26 (7): 1680–1683. PMID 21425331. doi:10.1002/jbmr.390.

[Fulzele_2010-8] Fulzele K, Riddle RC, DiGirolamo DJ, Cao X, Wan C, Chen D, Faugere MC, Aja S, Hussain MA, Brüning JC, Clemens TL. Insulin receptor signaling in osteoblasts regulates postnatal bone acquisition and body composition. Cell. July 2010, 142 (2): 309–19. PMC 2925155  . PMID 20655471. doi:10.1016/j.cell.2010.06.002.

[bone_turnover-9] Bharadwaj S, Naidu AG, Betageri GV, Prasadarao NV, Naidu AS. Milk ribonuclease-enriched lactoferrin induces positive effects on bone turnover markers in postmenopausal women. Osteoporos Int. September 2009, 20 (9): 1603–11. PMID 19172341. doi:10.1007/s00198-009-0839-8.

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