骨钙蛋白

Bone gamma-carboxyglutamate (gla) protein
骨含伽马羧酸蛋白
Bone gamma-carboxyglutamate (gla) protein; 骨含伽马羧酸蛋白
	PDB rendering based on 1q8h.
有效结构
PDB	直系同源检索：PDBe, RCSB
PDB查询代码列表
	1q3m, 1q8h
标识
代号	BGLAP; BGP; OC; OCN
扩展标识	遗传学：112260 鼠基因：88156 同源基因：104130 GeneCards: BGLAP Gene
基因本体论描述
分子功能	· structural molecule activity; · calcium ion binding; · structural constituent of bone; · hydroxyapatite binding;
细胞成分	· extracellular region; · extracellular space; · rough endoplasmic reticulum; · Golgi apparatus; · dendrite; · membrane-bounded vesicle; · perikaryon;
生物过程	· 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
直系同源体
物种	人类
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查询	[1]
	查; 论; 编;

骨钙蛋白，也被称为骨含伽马羧酸蛋白 (BGLAP)，是一种非胶原蛋白质，可见于骨或牙本质之中。因其含伽马羧酸基团, 所以其合成是维生素K依赖性的。在人体，骨钙蛋白是由BGLAP 基因编码的。^[1]^[2] 其受体是 GPRC6A.^[3]

功能

骨钙蛋白仅由成骨细胞分泌，它在人体代谢调节方面有一定作用，并具有“促成骨”作用。^[4] 它也涉及骨矿化和钙离子动态平衡。骨钙蛋白在人体内也是一种荷尔蒙，它可促使胰腺的beta细胞释放更多的胰岛素, 并同时指示脂肪细胞释放荷尔蒙脂联素来提高对胰岛素的敏感性。^[4]

当前的数据暗示骨钙蛋白在男性生育能力方面扮演的一种可能的角色。^[5] 来自哥伦比亚大学医学中心的研究提出骨钙蛋白可能增强睾酮的分泌。^[6] 虽然这些研究只由单独的一家实验室进行，但至少有其它两个团体曾独立确认了骨钙蛋白在胰岛素分泌方面的作用。^[7]^[8]

用做成骨过程的生化标记

由于骨钙蛋白是由成骨细胞产生，所以它常常被用作成骨过程标记。在使用针对成骨细胞的成骨促进药物，如特立帕肽(Teriparatide)的治疗过程当中，曾观察到较高的血浆骨钙蛋白水平与骨矿物质密度（BMD）之间有较高的相关性。在许多研究当中，骨钙蛋白被用作一种指示某种药物骨形成效应的基本的生化标记。例如，一项针对一种叫做乳铁蛋白(lactoferrin)的糖蛋白对成骨过程效用的研究就使用了骨钙蛋白作为成骨细胞活跃度的度量指标。^[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. 请检查|date=中的日期值 (帮助)
^ 存档副本. [2014-10-18]. （原始内容存档于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.骨骼对男性生育力的内分泌调节（Endocrine Regulation of Male Fertility by the Skeleton）. Cell, 17 February 2011 doi:10.1016/j.cell.2011.02.004
^ 睾酮
^ 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.

延伸阅读

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.

外部链接

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. 请检查|date=中的日期值 (帮助)

[3] 存档副本. [2014-10-18]. （原始内容存档于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.骨骼对男性生育力的内分泌调节（Endocrine Regulation of Male Fertility by the Skeleton）. Cell, 17 February 2011 doi:10.1016/j.cell.2011.02.004

[6] 睾酮

[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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