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Bglap  -  bone gamma-carboxyglutamate (gla) protein

Rattus norvegicus

Synonyms: BGP, Bglap2, Bgp, Bgpr, Bgpra, ...
 
 
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Disease relevance of Bglap2

 

High impact information on Bglap2

  • Structural requirements for parathyroid hormone action in mature bone. Effects on release of cyclic adenosine monophosphate and bone gamma-carboxyglutamic acid-containing protein from perfused rat hindquarters [6].
  • The cDNAs have also allowed isolation of the human BGP gene; analysis of this gene indicates the presence of four exons [7].
  • By sequencing several cloned cDNAs, we have established a 489-base-pair sequence that predicts a mature BGP of 50 amino acid residues with an NH2-terminal extension of 49 residues [1].
  • A stretch of 9 residues proximal to the NH2 terminus of secreted BGP is strikingly similar to the corresponding regions in known propeptides of the gamma-carboxyglutamic acid-containing blood coagulation factors [1].
  • Rats maintained for 8 months on a level of warfarin sufficient to decrease the vitamin K-dependent protein of bone (bone Gla protein) to 2% of normal have an excessive mineralization disorder characterized by complete fusion of the proximal tibial growth plate and cessation of longitudinal growth [8].
 

Chemical compound and disease context of Bglap2

 

Biological context of Bglap2

 

Anatomical context of Bglap2

  • This is only the second example of a bone matrix protein whose synthesis is dramatically increased by vitamin D, the first being the 6-fold stimulation of BGP synthesis by 1,25(OH)2D3 in ROS 17/2 cells [15].
  • Similar results were obtained from the analysis of the longitudinal distribution of MGP and BGP in 14-day-old rat tibia, a bone in which new mineral is added rapidly at both growth plates [16].
  • There was no correlation between the expression of BGP by osteoblasts and the morphological aspect of these cells, their apparent degree of polarization with respect to the bone matrix, or their relation with the mineralized phase [17].
  • The ratios of BGP contents of young bone marrow/HA to old bone marrow/HA composite in young and old recipients were about nine and eight times, respectively [18].
  • The assay has been used to confirm the BGP mRNA changes with hormonal treatment in cultured cells and the age-related changes in whole tibia in vivo [19].
 

Associations of Bglap2 with chemical compounds

  • The sequence of the rat BGP gene was compared to that of the recently published human BGP gene (Celeste et al., EMBO J. 5, 1885, 1986) [13].
  • We have previously shown that TNF-alpha inhibits 1,25-(OH)2D3-stimulated synthesis of bone gla protein (BGP), an abundant and osteoblast-specific matrix constituent [20].
  • We conclude that, although both triamcinolone acetate and retinoic acid increase the 1,25-dihydroxyvitamin D3 stimulation of BGP secretion by ROS 17/2 cells, they have different effects on the regulation of collagen production [9].
  • The levels of serum testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH), serum bone Gla-protein (BGP) and tartrate-resistant acid phosphatase activity in serum (StrACP) were determined [14].
  • In contrast, the protein synthesis inhibitor cycloheximide blocked BGP synthesis in both untreated and 1,25-(OH)2D3-treated cells [10].
 

Regulatory relationships of Bglap2

 

Other interactions of Bglap2

  • Cells in fractions IV, V and VI exhibited striking responses; the levels of cAMP and insulin-like growth factor I, bone Gla protein, and mineral accumulation were significantly elevated in the stretched cells [22].
  • Rats receiving CsA (groups 2 and 4) had elevated levels of 1,25-dihydroxyvitamin D and bone gla protein, whereas rats receiving IFN gamma alone (group 3) had no change in levels of these parameters [23].
  • High-dose OCT increased serum ionized calcium (P less than 0.05) and decreased serum parathyroid hormone (PTH) (P less than 0.05) at all time points and increased serum bone Gla protein on days 7 and 28 (P less than 0.05) compared with controls [24].
  • In contrast to osteocalcin (bone Gla protein), this increase was not dependent on mineralization but was related to the extent of differentiation associated with and potentially induced by extracellular matrix formation [25].
  • On the other hand, Northern blot analysis showed a different pattern of expression for the genes, c-fos, c-jun, c-Ha-ras, transin (rat stromelysin), bone Gla protein (osteocalsin) and nm23/NDP kinase [26].
 

Analytical, diagnostic and therapeutic context of Bglap2

References

  1. The propeptide of rat bone gamma-carboxyglutamic acid protein shares homology with other vitamin K-dependent protein precursors. Pan, L.C., Price, P.A. Proc. Natl. Acad. Sci. U.S.A. (1985) [Pubmed]
  2. Circulating levels and bone contents of bone gamma-carboxyglutamic acid-containing protein are decreased in streptozocin-induced diabetes. Possible marker for diabetic osteopenia. Ishida, H., Seino, Y., Taminato, T., Usami, M., Takeshita, N., Seino, Y., Tsutsumi, C., Moriuchi, S., Akiyama, Y., Hara, K. Diabetes (1988) [Pubmed]
  3. Bone Gla protein messenger ribonucleic acid is regulated by both 1,25-dihydroxyvitamin D3 and 3',5'-cyclic adenosine monophosphate in rat osteosarcoma cells. Theofan, G., Price, P.A. Mol. Endocrinol. (1989) [Pubmed]
  4. 1,25-Dihydroxyvitamin D3 modulates glucocorticoid-induced alteration in serum bone Gla protein and bone histomorphometry. Jowell, P.S., Epstein, S., Fallon, M.D., Reinhardt, T.A., Ismail, F. Endocrinology (1987) [Pubmed]
  5. Vitamin K-dependent carboxylase in skin. de Boer-van den Berg, M.A., Verstijnen, C.P., Vermeer, C. J. Invest. Dermatol. (1986) [Pubmed]
  6. Structural requirements for parathyroid hormone action in mature bone. Effects on release of cyclic adenosine monophosphate and bone gamma-carboxyglutamic acid-containing protein from perfused rat hindquarters. Calvo, M.S., Fryer, M.J., Laakso, K.J., Nissenson, R.A., Price, P.A., Murray, T.M., Heath, H. J. Clin. Invest. (1985) [Pubmed]
  7. Isolation of the human gene for bone gla protein utilizing mouse and rat cDNA clones. Celeste, A.J., Rosen, V., Buecker, J.L., Kriz, R., Wang, E.A., Wozney, J.M. EMBO J. (1986) [Pubmed]
  8. Excessive mineralization with growth plate closure in rats on chronic warfarin treatment. Price, P.A., Williamson, M.K., Haba, T., Dell, R.B., Jee, W.S. Proc. Natl. Acad. Sci. U.S.A. (1982) [Pubmed]
  9. Retinoic acid and glucocorticoids enhance the effect of 1,25-dihydroxyvitamin D3 on bone gamma-carboxyglutamic acid protein synthesis by rat osteosarcoma cells. Nishimoto, S.K., Salka, C., Nimni, M.E. J. Bone Miner. Res. (1987) [Pubmed]
  10. The effect of transcriptional inhibitors on the bone gamma-carboxyglutamic acid protein response to 1,25-dihydroxyvitamin D3 in osteosarcoma cells. Pan, L.C., Price, P.A. J. Biol. Chem. (1984) [Pubmed]
  11. Sequence of the precursor to rat bone gamma-carboxyglutamic acid protein that accumulates in warfarin-treated osteosarcoma cells. Pan, L.C., Williamson, M.K., Price, P.A. J. Biol. Chem. (1985) [Pubmed]
  12. Tumor necrosis factor-alpha inhibits 1,25-dihydroxyvitamin D3-stimulated bone Gla protein synthesis in rat osteosarcoma cells (ROS 17/2.8) by a pretranslational mechanism. Nanes, M.S., Rubin, J., Titus, L., Hendy, G.N., Catherwood, B. Endocrinology (1991) [Pubmed]
  13. Molecular structure of the rat bone Gla protein gene and identification of putative regulatory elements. Theofan, G., Haberstroh, L.M., Price, P.A. DNA (1989) [Pubmed]
  14. The testosterone mimetic properties of icariin. Zhang, Z.B., Yang, Q.T. Asian J. Androl. (2006) [Pubmed]
  15. 1,25-Dihydroxyvitamin D3 stimulates the synthesis of matrix gamma-carboxyglutamic acid protein by osteosarcoma cells. Mutually exclusive expression of vitamin K-dependent bone proteins by clonal osteoblastic cell lines. Fraser, J.D., Otawara, Y., Price, P.A. J. Biol. Chem. (1988) [Pubmed]
  16. Developmental appearance of matrix GLA protein during calcification in the rat. Otawara, Y., Price, P.A. J. Biol. Chem. (1986) [Pubmed]
  17. A comparative immunocytochemical study on the subcellular distributions of 44 kDa bone phosphoprotein and bone gamma-carboxyglutamic acid (Gla)-containing protein in osteoblasts. Mark, M.P., Prince, C.W., Gay, S., Austin, R.L., Bhown, M., Finkelman, R.D., Butler, W.T. J. Bone Miner. Res. (1987) [Pubmed]
  18. The effect of aging on bone formation in porous hydroxyapatite: biochemical and histological analysis. Inoue, K., Ohgushi, H., Yoshikawa, T., Okumura, M., Sempuku, T., Tamai, S., Dohi, Y. J. Bone Miner. Res. (1997) [Pubmed]
  19. Rapid and sensitive method of quantitation of bone gla protein mRNA using competitive polymerase chain reaction. Araki, N., Robinson, F.D., Nishimoto, S.K. J. Bone Miner. Res. (1993) [Pubmed]
  20. Tumor necrosis factor alpha decreases 1,25-dihydroxyvitamin D3 receptors in osteoblastic ROS 17/2.8 cells. Mayur, N., Lewis, S., Catherwood, B.D., Nanes, M.S. J. Bone Miner. Res. (1993) [Pubmed]
  21. Interferon-gamma inhibits 1,25-dihydroxyvitamin D3-stimulated synthesis of bone GLA protein in rat osteosarcoma cells by a pretranslational mechanism. Nanes, M.S., Rubin, J., Titus, L., Hendy, G.N., Catherwood, B.D. Endocrinology (1990) [Pubmed]
  22. Distinct responses of different populations of bone cells to mechanical stress. Mikuni-Takagaki, Y., Suzuki, Y., Kawase, T., Saito, S. Endocrinology (1996) [Pubmed]
  23. Interferon-gamma causes loss of bone volume in vivo and fails to ameliorate cyclosporin A-induced osteopenia. Mann, G.N., Jacobs, T.W., Buchinsky, F.J., Armstrong, E.C., Li, M., Ke, H.Z., Ma, Y.F., Jee, W.S., Epstein, S. Endocrinology (1994) [Pubmed]
  24. The effect of a new vitamin D analog, 22-oxa-1 alpha,25(OH)2D3, on bone mineral metabolism in normal male rats. Takizawa, M., Fallon, M., Stein, B., Epstein, S. Calcif. Tissue Int. (1992) [Pubmed]
  25. Developmental expression and hormonal regulation of the rat matrix Gla protein (MGP) gene in chondrogenesis and osteogenesis. Barone, L.M., Owen, T.A., Tassinari, M.S., Bortell, R., Stein, G.S., Lian, J.B. J. Cell. Biochem. (1991) [Pubmed]
  26. Heterogeneous pattern of gene expression in cloned cell lines established from a rat transplantable osteosarcoma lung metastatic nodule. Honoki, K., Mori, T., Tsutsumi, M., Tsujiuchi, T., Kido, A., Morishita, T., Miyauchi, Y., Dohi, Y., Mii, Y., Tamai, S., Konishi, Y. Cancer Lett. (1998) [Pubmed]
  27. The identification of matrix Gla protein in cartilage. Hale, J.E., Fraser, J.D., Price, P.A. J. Biol. Chem. (1988) [Pubmed]
  28. Secretion of the vitamin K-dependent protein of bone by rat osteosarcoma cells. Evidence for an intracellular precursor. Nishimoto, S.K., Price, P.A. J. Biol. Chem. (1980) [Pubmed]
  29. Influence of age on cyclosporin A-induced alterations in bone mineral metabolism in the rat in vivo. Katz, I., Li, M., Joffe, I., Stein, B., Jacobs, T., Liang, X.G., Ke, H.Z., Jee, W., Epstein, S. J. Bone Miner. Res. (1994) [Pubmed]
 
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