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Gene Review

BGLAP  -  bone gamma-carboxyglutamate (gla) protein

Gallus gallus

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Disease relevance of LOC396348

  • The in vitro effects on human promyeloid leukemia (HL-60 cell) differentiation and osteocalcin secretion by human osteosarcoma (MG-63) cells by 1 alpha, 25-(OH)2-19-nor-D3 were nearly identical to those of 1 alpha-25-(OH)2D3, whereas 19-nor-previtamin D3 showed poor activity (2%) [1].
  • Nuclear extracts from cells infected with the hVDR-expressing adenoviruses contain an activity that specifically binds an oligonucleotide with sequences from the rat osteocalcin vitamin D3 response element, as determined by gel mobility shift [2].
  • In the vitamin D-deficient animals, osteomalacia was evident histologically by 7 weeks, at which time serum 1,25-(OH)2D3 was not detectable, bone osteocalcin was decreased by 50%, and serum osteocalcin was decreased by 20% [3].
  • To evaluate whether this decrease in bone osteocalcin was due directly to the decrease or absence of vitamin D and its metabolites or to the secondary hypocalcemia and osteomalacia or other changes accompanying the deficiency of vitamin D, three experimental groups of Holtzman rats were studied [3].
  • Binding of CBFalpha/AML/PEBP2alpha (core binding factor alpha/acute myelogenous leukemia/polyoma enhancer binding protein 2alpha) proteins is a key event in both tissue-specific and developmentally regulated osteocalcin (OC) promoter activity [4].

High impact information on LOC396348

  • Ank-overexpressing hypertrophic nonmineralizing growth plate chondrocytes showed decreased intra- and extracellular PP(i) levels; increased mineralization-related gene expression of APase, type I collagen, and osteocalcin; increased APase activity; and mineralization [5].
  • Despite the pro-osteogenic effects of Ihh on periosteal cell differentiation, mechanical articulation of the quadratojugal/quadrate joint in explant culture revealed a negative role for articulation in the regulation of osteocalcin by germinal region descendants [6].
  • 1 beta,25-(OH)2D3 was a potent antagonist of 1 alpha,25-(OH)2D3-mediated transcaltachia and 45Ca2+ uptake in ROS 17/2.8 cells but was unable to block the genomic 1 alpha,25-(OH)2D3 induction of chick calbindin-D28k (in vivo), induction of MG-63 cell osteocalcin, and HL-60 cell differentiation [7].
  • Chicken osteocalcin shares many structural features, including the sequence positions of its 3 gamma-carboxyglutamic acid (Gla) residues, with osteocalcins of human, monkey, cow, and rat, but is cryptic in the radioimmunoassays for these species [8].
  • Osteocalcin appears coincident with the very earliest detectable perichondral mineralization in developing long bone (tibiotarsus) of the 7- to 8-day-old chick embryo (stages 31-33) [8].

Chemical compound and disease context of LOC396348

  • After transient transfection into the osteoblast-like rat osteosarcoma cell line ROS 17/2.8, the BGP promoter demonstrated a low level of basal activity that was increased approximately 10-fold by the addition of 10(-8) M 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] [9].

Biological context of LOC396348


Anatomical context of LOC396348


Associations of LOC396348 with chemical compounds

  • The complete primary structure of osteocalcin, the gamma-carboxyglutamic acid (Gla)-containing calcium-binding protein isolated from chicken bone has been determined by gas chromatographic mass spectrometry [15].
  • The 48-amino-acid pre-pro-peptide contains the expected hydrophobic leader sequence and the dibasic Lys-Arg sequence preceding the NH2-terminal His of the mature 49-amino-acid chicken osteocalcin, which is believed to be necessary for pro-peptide cleavage [13].
  • First, extraction and gel filtration in 4 M guanidine hydrochloride of total bone proteins has revealed high molecular weight species which share antigenic determinants with osteocalcin, namely, 10,000 (+/- 1,000), 15,000 (+/- 2,000), 35,000 (+/- 5,000), and 85,000 (+/- 15,000), in addition to 5,670 osteocalcin [8].
  • These bases, which are essential for the 1,25-(OH)2D3 responsiveness of the rat osteocalcin gene, are also present in a similar position, relative to the VDRE, in the human osteocalcin gene [12].
  • In contrast, osteocalcin levels, alkaline phosphatase activity, and total calcium levels showed a dose-related decrease in cultures treated with caffeine [16].

Physical interactions of LOC396348


Regulatory relationships of LOC396348


Other interactions of LOC396348


Analytical, diagnostic and therapeutic context of LOC396348


  1. Biologic activity of dihydroxylated 19-nor-(pre)vitamin D3. Bouillon, R., Sarandeses, L.A., Allewaert, K., Zhao, J., Mascareñas, J.L., Mouriño, A., Vrielynck, S., de Clercq, P., Vandewalle, M. J. Bone Miner. Res. (1993) [Pubmed]
  2. Overexpression of the human vitamin D3 receptor in mammalian cells using recombinant adenovirus vectors. Smith, C.L., Hager, G.L., Pike, J.W., Marx, S.J. Mol. Endocrinol. (1991) [Pubmed]
  3. Bone and serum concentrations of osteocalcin as a function of 1,25-dihydroxyvitamin D3 circulating levels in bone disorders in rats. Lian, J.B., Carnes, D.L., Glimcher, M.J. Endocrinology (1987) [Pubmed]
  4. Interaction of CBF alpha/AML/PEBP2 alpha transcription factors with nucleosomes containing promoter sequences requires flexibility in the translational positioning of the histone octamer and exposure of the CBF alpha site. Gutiérrez, J., Sierra, J., Medina, R., Puchi, M., Imschenetzky, M., van Wijnen, A., Lian, J., Stein, G., Stein, J., Montecino, M. Biochemistry (2000) [Pubmed]
  5. Role of the progressive ankylosis gene (ank) in cartilage mineralization. Wang, W., Xu, J., Du, B., Kirsch, T. Mol. Cell. Biol. (2005) [Pubmed]
  6. Secondary chondrocyte-derived Ihh stimulates proliferation of periosteal cells during chick development. Buxton, P.G., Hall, B., Archer, C.W., Francis-West, P. Development (2003) [Pubmed]
  7. Demonstration that 1 beta,25-dihydroxyvitamin D3 is an antagonist of the nongenomic but not genomic biological responses and biological profile of the three A-ring diastereomers of 1 alpha,25-dihydroxyvitamin D3. Norman, A.W., Bouillon, R., Farach-Carson, M.C., Bishop, J.E., Zhou, L.X., Nemere, I., Zhao, J., Muralidharan, K.R., Okamura, W.H. J. Biol. Chem. (1993) [Pubmed]
  8. Presence of osteocalcin and related higher molecular weight 4-carboxyglutamic acid-containing proteins in developing bone. Hauschka, P.V., Frenkel, J., DeMuth, R., Gundberg, C.M. J. Biol. Chem. (1983) [Pubmed]
  9. The vitamin D-responsive element in the rat bone Gla protein gene is an imperfect direct repeat that cooperates with other cis-elements in 1,25-dihydroxyvitamin D3- mediated transcriptional activation. Terpening, C.M., Haussler, C.A., Jurutka, P.W., Galligan, M.A., Komm, B.S., Haussler, M.R. Mol. Endocrinol. (1991) [Pubmed]
  10. Spaceflight effects on cultured embryonic chick bone cells. Landis, W.J., Hodgens, K.J., Block, D., Toma, C.D., Gerstenfeld, L.C. J. Bone Miner. Res. (2000) [Pubmed]
  11. Isolation and complete amino acid sequence of osteocalcin from canine bone. Colombo, G., Fanti, P., Yao, C., Malluche, H.H. J. Bone Miner. Res. (1993) [Pubmed]
  12. DNA sequences downstream from the vitamin D response element of the rat osteocalcin gene are required for ligand-dependent transactivation. Sneddon, W.B., Bogado, C.E., Kiernan, M.S., Demay, M.B. Mol. Endocrinol. (1997) [Pubmed]
  13. Characterization of structural sequences in the chicken osteocalcin gene: expression of osteocalcin by maturing osteoblasts and by hypertrophic chondrocytes in vitro. Neugebauer, B.M., Moore, M.A., Broess, M., Gerstenfeld, L.C., Hauschka, P.V. J. Bone Miner. Res. (1995) [Pubmed]
  14. Correlation of an osteoclast antigen and ruffled border on giant cells formed in response to resorbable substrates. Webber, D., Osdoby, P., Hauschka, P., Krukowski, M. J. Bone Miner. Res. (1990) [Pubmed]
  15. Gas chromatographic mass spectrometric sequence determination of osteocalcin, a gamma-carboxyglutamic acid-containing protein from chicken bone. Carr, S.A., Hauschka, P.V., Biemann, K. J. Biol. Chem. (1981) [Pubmed]
  16. Effect of caffeine on parameters of osteoblast growth and differentiation of a mineralized extracellular matrix in vitro. Tassinari, M.S., Gerstenfeld, L.C., Stein, G.S., Lian, J.B. J. Bone Miner. Res. (1991) [Pubmed]
  17. Specific binding to vitamin D response elements of chicken intestinal DNA-binding activity is not related to the vitamin D receptor. Ferrari, S., Battini, R., Molinari, S. Mol. Endocrinol. (1994) [Pubmed]
  18. Regulation of proliferation and osteochondrogenic differentiation of periosteum-derived cells by transforming growth factor-beta and basic fibroblast growth factor. Iwasaki, M., Nakahara, H., Nakata, K., Nakase, T., Kimura, T., Ono, K. The Journal of bone and joint surgery. American volume. (1995) [Pubmed]
  19. Annexin V and terminal differentiation of growth plate chondrocytes. Wang, W., Xu, J., Kirsch, T. Exp. Cell Res. (2005) [Pubmed]
  20. Overexpression of Dlx5 in chicken calvarial cells accelerates osteoblastic differentiation. Tadic, T., Dodig, M., Erceg, I., Marijanovic, I., Mina, M., Kalajzic, Z., Velonis, D., Kronenberg, M.S., Kosher, R.A., Ferrari, D., Lichtler, A.C. J. Bone Miner. Res. (2002) [Pubmed]
  21. 25-Dehydro-1alpha-hydroxyvitamin D3-26,23S-lactone antagonizes the nuclear vitamin D receptor by mediating a unique noncovalent conformational change. Bula, C.M., Bishop, J.E., Ishizuka, S., Norman, A.W. Mol. Endocrinol. (2000) [Pubmed]
  22. Selective extractability of noncollagenous proteins from chicken bone. Gerstenfeld, L.C., Feng, M., Gotoh, Y., Glimcher, M.J. Calcif. Tissue Int. (1994) [Pubmed]
  23. Characteristics and culture of osteoblasts derived from avian long bone. Gay, C.V., Lloyd, Q.P., Gilman, V.R. In Vitro Cell. Dev. Biol. Anim. (1994) [Pubmed]
  24. Demonstration of reduced mitogenic and osteoinductive activities in demineralized allogeneic bone matrix from vitamin D-deficient rats. Turner, R.T., Farley, J., Vandersteenhoven, J.J., Epstein, S., Bell, N.H., Baylink, D.J. J. Clin. Invest. (1988) [Pubmed]
  25. Calcium-dependent alpha-helical structure in osteocalcin. Hauschka, P.V., Carr, S.A. Biochemistry (1982) [Pubmed]
  26. Concentrations of osteocalcin and phosphoprotein as a function of mineral content and age in cortical bone. Lian, J.B., Roufosse, A.H., Reit, B., Glimcher, M.J. Calcif. Tissue Int. (1982) [Pubmed]
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