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Gene Review

Bglap  -  bone gamma carboxyglutamate protein

Mus musculus

Synonyms: BGP, Bglap1, Bone Gla protein, Gamma-carboxyglutamic acid-containing protein, OC, ...
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Disease relevance of Bglap1

  • Osteopenia was associated with mechanical fragility, manifested by decreased stiffness and mechanical load at fracture, and was caused by suppressed bone formation, indicated by decreased cancellous double-labeled surface, mineralizing surface, serum osteocalcin level, and mineralized nodule number in bone marrow stromal cell cultures [1].
  • cDNAs which encode bone gla protein (BGP), an abundant gamma-carboxylated protein of bone, have been cloned from rat and mouse osteosarcoma cell lines [2].
  • Higher levels of mRNAs for type X collagen, bone Gla protein, and osteopontin were found at nonpermissive temperatures, suggesting that the expression of these genes was upregulated upon growth arrest, as is the case in vivo during chondrocyte hypertrophy [3].
  • The OC promoter region -154 to -90 confers FGF2/FSK responsiveness on the Rous sarcoma virus minimal promoter [4].
  • These data thereby show a dissociation between osteocalcin production and bone resorption [5].

Psychiatry related information on Bglap1

  • Plasma osteocalcin, a marker of osteoblastic activity, is reduced in starvation, malnutrition, and anorexia nervosa, resulting in low bone turnover osteoporosis [6].

High impact information on Bglap1


Chemical compound and disease context of Bglap1


Biological context of Bglap1


Anatomical context of Bglap1

  • This paper examines the role of the alpha2-integrin subunit in osteocalcin promoter activation and osteoblast differentiation [20].
  • Osteocalcin (OC) is a matrix calcium-binding protein expressed in osteoblasts and odontoblasts undergoing mineralization [21].
  • By the late appositional phases of E18.5 and neonatal teeth, Osc mRNA is highly expressed in mature columnar odontoblasts adjacent to accumulating dentin [22].
  • The persistence of cbfa1 and ihh, and their targets osteocalcin and gli1, in the callus suggests comparable processes of chondrocyte maturation and specification of a neo-perichondrium occur following injury [23].
  • In addition to expression of genes associated with cementoblasts, OC/CM cells promoted mineral nodule formation and exhibited a PTHrP mediated cAMP response [24].

Associations of Bglap1 with chemical compounds

  • This study illustrates that 1,25-(OH)2D3 can play different roles in the expression of the same gene in various species and indicates that this regulation in mouse occurs through an indirect mechanism, 1,25-(OH)2D3 acting on a gene genetically located upstream of Osteocalcin [18].
  • Because standard (short-term) transient transfection assays with OC promoter-reporter constructs did not recapitulate the strong DEX-mediated repression, mapping of OC negative glucocorticoid response elements (GREs) was performed initially by stable transfection and then with long-term transient transfection assays [25].
  • Previous work showed that collagen matrix synthesis, induced by addition of ascorbic acid to cells, precedes and is essential for the expression of osteoblast markers and induction of the osteocalcin promoter in murine MC3T3-E1 cells [20].
  • Treatment of MC3T3-E1 osteoblasts and ROS 17/2.8 cells stably transfected with PPARgamma2 with the PPARgamma activator 15-deoxy-Delta12,14-prostaglandin J2 inhibited the mRNA expression of osteocalcin and Runx2, the latter of which is a key transcription factor in osteoblast differentiation [26].
  • Expression of Msx2 decreases basal activity of the 1-kilobase (-1050 to +32) rat OC promoter by 80%; however, the promoter is still inducible 3-fold by calcitriol [21].

Regulatory relationships of Bglap1

  • Transfection studies show BMP-2 suppresses OC promoter activity in C2C12, but not in osteoblastic ROS 17/2.8 cells [27].

Other interactions of Bglap1

  • We named them osteocalcin gene 1 (OG1), osteocalcin gene 2 (OG2), and osteocalcin-related gene (ORG) in order from the 5' end to the 3' end of the cluster [17].
  • Maximal suppression of OC promoter activity in response to BMP-2 requires sequences in the proximal promoter (up to nt -365) and may occur independent of the three Cbfa sites [27].
  • Hybridization of polymerase chain reaction-amplified cDNAs with specific oligonucleotides and RNase protection assays showed that OG1 and OG2 are expressed only in bone, whereas ORG is transcribed in kidney but not in bone [17].
  • T3 significantly increased osteoblast 3H-proline incorporation, alkaline phosphatase (ALP), and osteocalcin [28].
  • Moreover, in cells exposed to dexamethasone, increases in AP and osteocalcin were accompanied by a repression of collagenase-1 expression [29].

Analytical, diagnostic and therapeutic context of Bglap1


  1. Interleukin 10-deficient mice develop osteopenia, decreased bone formation, and mechanical fragility of long bones. Dresner-Pollak, R., Gelb, N., Rachmilewitz, D., Karmeli, F., Weinreb, M. Gastroenterology (2004) [Pubmed]
  2. 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]
  3. Type X collagen gene expression in mouse chondrocytes immortalized by a temperature-sensitive simian virus 40 large tumor antigen. Lefebvre, V., Garofalo, S., de Crombrugghe, B. J. Cell Biol. (1995) [Pubmed]
  4. Synergistic induction of osteocalcin gene expression: identification of a bipartite element conferring fibroblast growth factor 2 and cyclic AMP responsiveness in the rat osteocalcin promoter. Boudreaux, J.M., Towler, D.A. J. Biol. Chem. (1996) [Pubmed]
  5. Regulation of osteocalcin production and bone resorption by 1,25-dihydroxyvitamin D3 in mouse long bones: interaction with the bone-derived growth factors TGF-beta and IGF-I. Staal, A., Geertsma-Kleinekoort, W.M., Van Den Bemd, G.J., Buurman, C.J., Birkenhäger, J.C., Pols, H.A., Van Leeuwen, J.P. J. Bone Miner. Res. (1998) [Pubmed]
  6. Leptin prevents the fall in plasma osteocalcin during starvation in male mice. Goldstone, A.P., Howard, J.K., Lord, G.M., Ghatei, M.A., Gardiner, J.V., Wang, Z.L., Wang, R.M., Girgis, S.I., Bailey, C.J., Bloom, S.R. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  7. Mice deficient in Abl are osteoporotic and have defects in osteoblast maturation. Li, B., Boast, S., de los Santos, K., Schieren, I., Quiroz, M., Teitelbaum, S.L., Tondravi, M.M., Goff, S.P. Nat. Genet. (2000) [Pubmed]
  8. Increased bone formation in osteocalcin-deficient mice. Ducy, P., Desbois, C., Boyce, B., Pinero, G., Story, B., Dunstan, C., Smith, E., Bonadio, J., Goldstein, S., Gundberg, C., Bradley, A., Karsenty, G. Nature (1996) [Pubmed]
  9. Increased bone formation and decreased osteocalcin expression induced by reduced Twist dosage in Saethre-Chotzen syndrome. Yousfi, M., Lasmoles, F., Lomri, A., Delannoy, P., Marie, P.J. J. Clin. Invest. (2001) [Pubmed]
  10. Gly369Cys mutation in mouse FGFR3 causes achondroplasia by affecting both chondrogenesis and osteogenesis. Chen, L., Adar, R., Yang, X., Monsonego, E.O., Li, C., Hauschka, P.V., Yayon, A., Deng, C.X. J. Clin. Invest. (1999) [Pubmed]
  11. Inhibition of osteoblastogenesis and promotion of apoptosis of osteoblasts and osteocytes by glucocorticoids. Potential mechanisms of their deleterious effects on bone. Weinstein, R.S., Jilka, R.L., Parfitt, A.M., Manolagas, S.C. J. Clin. Invest. (1998) [Pubmed]
  12. Osteocalcin promoter-based toxic gene therapy for the treatment of osteosarcoma in experimental models. Ko, S.C., Cheon, J., Kao, C., Gotoh, A., Shirakawa, T., Sikes, R.A., Karsenty, G., Chung, L.W. Cancer Res. (1996) [Pubmed]
  13. Melatonin promotes osteoblast differentiation and bone formation. Roth, J.A., Kim, B.G., Lin, W.L., Cho, M.I. J. Biol. Chem. (1999) [Pubmed]
  14. Picomolar norethindrone in vitro stimulates the cell proliferation and activity of a human osteosarcoma cell line and increases bone collagen synthesis without an effect on bone resorption. Lau, K.H., Wang, S.P., Linkhart, T.A., Demarest, K.T., Baylink, D.J. J. Bone Miner. Res. (1994) [Pubmed]
  15. Imbalance of local bone metabolism in inflammatory arthritis and its reversal upon tumor necrosis factor blockade: direct analysis of bone turnover in murine arthritis. Zwerina, J., Tuerk, B., Redlich, K., Smolen, J.S., Schett, G. Arthritis Res. Ther. (2006) [Pubmed]
  16. Functional hierarchy between two OSE2 elements in the control of osteocalcin gene expression in vivo. Frendo, J.L., Xiao, G., Fuchs, S., Franceschi, R.T., Karsenty, G., Ducy, P. J. Biol. Chem. (1998) [Pubmed]
  17. The mouse osteocalcin gene cluster contains three genes with two separate spatial and temporal patterns of expression. Desbois, C., Hogue, D.A., Karsenty, G. J. Biol. Chem. (1994) [Pubmed]
  18. 1,25-dihydroxyvitamin D3 inhibits Osteocalcin expression in mouse through an indirect mechanism. Zhang, R., Ducy, P., Karsenty, G. J. Biol. Chem. (1997) [Pubmed]
  19. MINT, the Msx2 interacting nuclear matrix target, enhances Runx2-dependent activation of the osteocalcin fibroblast growth factor response element. Sierra, O.L., Cheng, S.L., Loewy, A.P., Charlton-Kachigian, N., Towler, D.A. J. Biol. Chem. (2004) [Pubmed]
  20. Role of the alpha2-integrin in osteoblast-specific gene expression and activation of the Osf2 transcription factor. Xiao, G., Wang, D., Benson, M.D., Karsenty, G., Franceschi, R.T. J. Biol. Chem. (1998) [Pubmed]
  21. Stimulus-selective inhibition of rat osteocalcin promoter induction and protein-DNA interactions by the homeodomain repressor Msx2. Newberry, E.P., Boudreaux, J.M., Towler, D.A. J. Biol. Chem. (1997) [Pubmed]
  22. Reciprocal temporospatial patterns of Msx2 and Osteocalcin gene expression during murine odontogenesis. Bidder, M., Latifi, T., Towler, D.A. J. Bone Miner. Res. (1998) [Pubmed]
  23. Does adult fracture repair recapitulate embryonic skeletal formation? Ferguson, C., Alpern, E., Miclau, T., Helms, J.A. Mech. Dev. (1999) [Pubmed]
  24. Employing a transgenic animal model to obtain cementoblasts in vitro. D'Errico, J.A., Berry, J.E., Ouyang, H., Strayhorn, C.L., Windle, J.J., Somerman, M.J. J. Periodontol. (2000) [Pubmed]
  25. Glucocorticoids inhibit osteocalcin transcription in osteoblasts by suppressing Egr2/Krox20-binding enhancer. Leclerc, N., Noh, T., Khokhar, A., Smith, E., Frenkel, B. Arthritis Rheum. (2005) [Pubmed]
  26. Activation of peroxisome proliferator-activated receptor-gamma inhibits the Runx2-mediated transcription of osteocalcin in osteoblasts. Jeon, M.J., Kim, J.A., Kwon, S.H., Kim, S.W., Park, K.S., Park, S.W., Kim, S.Y., Shin, C.S. J. Biol. Chem. (2003) [Pubmed]
  27. Transient upregulation of CBFA1 in response to bone morphogenetic protein-2 and transforming growth factor beta1 in C2C12 myogenic cells coincides with suppression of the myogenic phenotype but is not sufficient for osteoblast differentiation. Lee, M.H., Javed, A., Kim, H.J., Shin, H.I., Gutierrez, S., Choi, J.Y., Rosen, V., Stein, J.L., van Wijnen, A.J., Stein, G.S., Lian, J.B., Ryoo, H.M. J. Cell. Biochem. (1999) [Pubmed]
  28. Insulin-like growth factor I production is essential for anabolic effects of thyroid hormone in osteoblasts. Huang, B.K., Golden, L.A., Tarjan, G., Madison, L.D., Stern, P.H. J. Bone Miner. Res. (2000) [Pubmed]
  29. Ascorbic acid induces collagenase-1 in human periodontal ligament cells but not in MC3T3-E1 osteoblast-like cells: potential association between collagenase expression and changes in alkaline phosphatase phenotype. Shiga, M., Kapila, Y.L., Zhang, Q., Hayami, T., Kapila, S. J. Bone Miner. Res. (2003) [Pubmed]
  30. Dlx3 transcriptional regulation of osteoblast differentiation: temporal recruitment of Msx2, Dlx3, and Dlx5 homeodomain proteins to chromatin of the osteocalcin gene. Hassan, M.Q., Javed, A., Morasso, M.I., Karlin, J., Montecino, M., van Wijnen, A.J., Stein, G.S., Stein, J.L., Lian, J.B. Mol. Cell. Biol. (2004) [Pubmed]
  31. Medium perfusion enhances osteogenesis by murine osteosarcoma cells in three-dimensional collagen sponges. Mueller, S.M., Mizuno, S., Gerstenfeld, L.C., Glowacki, J. J. Bone Miner. Res. (1999) [Pubmed]
  32. Groucho/TLE/R-esp proteins associate with the nuclear matrix and repress RUNX (CBF(alpha)/AML/PEBP2(alpha)) dependent activation of tissue-specific gene transcription. Javed, A., Guo, B., Hiebert, S., Choi, J.Y., Green, J., Zhao, S.C., Osborne, M.A., Stifani, S., Stein, J.L., Lian, J.B., van Wijnen, A.J., Stein, G.S. J. Cell. Sci. (2000) [Pubmed]
  33. Chondrocytes provide morphogenic signals that selectively induce osteogenic differentiation of mesenchymal stem cells. Gerstenfeld, L.C., Cruceta, J., Shea, C.M., Sampath, K., Barnes, G.L., Einhorn, T.A. J. Bone Miner. Res. (2002) [Pubmed]
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