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Gene Review

BGLAP  -  bone gamma-carboxyglutamate (gla) protein

Homo sapiens

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

  • Osteocalcin: genetic and physical mapping of the human gene BGLAP and its potential role in postmenopausal osteoporosis [1].
  • Urinary hydroxyproline (r = 0.29, P less than 0.001), an index of bone resorption, and serum alkaline phosphatase (r = 0.31, P less than 0.001), an index of bone formation, also increased with age and these increases correlated with increases in serum BGP (r = 0.39, P less than 0.001 and r = 0.43, P less than 0.001, respectively) [2].
  • A subgroup of 32 women who were found to have vertebral fractures, hip fractures, or both had significantly higher values for serum BGP than the remainder [2].
  • Because it is unclear whether age-related bone loss results from increased bone resorption, decreased bone formation or both, we measured the serum level of bone Gla-protein (BGP), a specific marker for bone turnover, in 174 women, ages 30 to 94 yr [2].
  • Only serum BGP showed a significant correlation in both sexes of the Cd-exposed subjects, and a sex difference was found in the relationship between bone metabolic markers and osteopenia [3].

High impact information on BGLAP


Chemical compound and disease context of BGLAP


Biological context of BGLAP

  • Through testing for association, linkage, and linkage and association simultaneously, our data support the VDR gene as a quantitative trait locus (QTL) underlying spine BMD variation and the BGP gene as a QTL underlying hip BMD variation [12].
  • In the present work, the BGP cDNA and gene were cloned from a teleost fish, Sparus aurata, and its tissue distribution, pattern of developmental expression and evolutionary pathways analyzed [13].
  • In addition to serum osteocalcin (BGP) we measured parathyroid hormone (PTH) (carboxyl and mid-molecule fragments), 25(OH)D, alkaline phosphatase, estradiol (E2), estrone (E1), dietary calcium intake, 24 hour urinary calcium excretion, and bone mineral density by CT scan of the lumbar vertebrae [14].
  • The different findings may reflect inter-population differences in the association (i.e., linkage disequilibrium) of molecular markers with BMD, and indicate the limit of using the HindIII marker of the BGP gene as a genetic marker to discern women susceptible to low BMD and thus osteoporosis in Chinese [15].
  • We did not find any significant difference in spine and hip BMD across BGP genotypes in either pre- or postmenopausal women or the combined group [15].

Anatomical context of BGLAP


Associations of BGLAP with chemical compounds

  • Using partial correlation coefficients, serum BGP still correlated positively with age (r = 0.31, P less than 0.001) after creatinine clearance was fixed but not with creatinine clearance (r = -0.04, NS) when age was fixed [2].
  • Serum immunoreactive parathyroid hormone concentrations (r = 0.39, P less than 0.001) and urinary cyclic AMP excretion (r = 0.38, P less than 0.001) increased, suggesting that PTH secretion increased with age; these increases correlated significantly with increases in serum BGP [2].
  • The time course of BGP digestion by each cathepsin was first determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis [20].
  • Accordingly, recent work indicates that, in mammalian bone, BGP is required for adequate maturation of the hydroxyapatite crystal [13].
  • Urinary excretion of BGP and hydroxyproline showed an increase in the anticonvulsant group, but it was not statistically significant [21].

Other interactions of BGLAP

  • Cathepsins B, L, H, and S readily cleave BGP at the G7-A8 bond; cathepsin L also cleaves at R43-R44; cathepsin B also cleaves at R44-F45; and cathepsin D cleaves only at A41-Y42 [20].
  • Phylogenetic analysis of the available BGP sequences supports the hypothesis that all BGPs have a single origin and share a common ancestor with a related vitamin K-dependent protein (Matrix Gla protein) [13].
  • However, in a subgroup of 10 patients without hyperparathyroidism, there was strong and significant correlation (r = 0.81, P less than 0.01) between BGP and BFR [22].
  • Compared with the non-exposed subjects, the levels of serum creatinine and BGP, urinary Cd and beta 2-microglobulin and blood Cd were higher, while the levels of serum inorganic phosphorus and MD indicators were lower in the Cd-exposed group [3].
  • Male RA patients showed decreased levels of serum BGP (7.3 +/- 1.0 vs 8.2 +/- 1.7 ng/mL; p < 0.01) [23].

Analytical, diagnostic and therapeutic context of BGLAP

  • The immunoreactivity of the major peptides generated by cathepsin cleavage was evaluated using the original radioimmunoassay developed for the detection of BGP in human serum [20].
  • These results demonstrate the utility of peptides generated by cathepsin digestion in the mapping of the antigenic epitopes recognized by a given BGP immunoassay [20].
  • We then incubated human and bovine BGP with each cathepsin for a sufficient time to reduce the level of intact protein by at least 20-fold, isolated the major cleavage peptides, and identified each by N-terminal sequence analysis and by amino acid analysis [20].
  • One week after the fracture, mean serum concentrations of calcium and ICTP were elevated in correspondence to degree of immobilization (mean Rankin score; 4.4), while serum concentrations of BGP, PTH, 25-OHD, and 1,25-[OH]2D were depressed [24].
  • Serum BGP and A1-P levels were significantly increased in the anticonvulsant group compared with the control group (P less than 0.05 and P less than 0.01, respectively), and a positive correlation was found between serum BGP and A1-P levels (P less than 0.05) [21].


  1. Osteocalcin: genetic and physical mapping of the human gene BGLAP and its potential role in postmenopausal osteoporosis. Raymond, M.H., Schutte, B.C., Torner, J.C., Burns, T.L., Willing, M.C. Genomics (1999) [Pubmed]
  2. Increase in serum bone gamma-carboxyglutamic acid protein with aging in women. Implications for the mechanism of age-related bone loss. Delmas, P.D., Stenner, D., Wahner, H.W., Mann, K.G., Riggs, B.L. J. Clin. Invest. (1983) [Pubmed]
  3. Assessment of cadmium-induced osteopenia by measurement of serum bone Gla protein, parathyroid hormone, and 1 alpha,25-dihydroxyvitamin D. Kido, T., Honda, R., Tsuritani, I., Ishizaki, M., Yamada, Y., Nogawa, K., Nakagawa, H., Dohi, Y. Journal of applied toxicology : JAT. (1991) [Pubmed]
  4. Serum and urinary markers of bone remodeling: assessment of bone turnover. Epstein, S. Endocr. Rev. (1988) [Pubmed]
  5. A mutation in the propeptide of Factor IX leads to warfarin sensitivity by a novel mechanism. Chu, K., Wu, S.M., Stanley, T., Stafford, D.W., High, K.A. J. Clin. Invest. (1996) [Pubmed]
  6. Sex steroids and bone mass. A study of changes about the time of menopause. Slemenda, C., Hui, S.L., Longcope, C., Johnston, C.C. J. Clin. Invest. (1987) [Pubmed]
  7. Serum bone gamma carboxyglutamic acid-containing protein in primary hyperparathyroidism and in malignant hypercalcemia. Comparison with bone histomorphometry. Delmas, P.D., Demiaux, B., Malaval, L., Chapuy, M.C., Edouard, C., Meunier, P.J. J. Clin. Invest. (1986) [Pubmed]
  8. Clinical significance of serum bone Gla protein and urinary gamma-Gla as biochemical markers in primary hyperparathyroidism. Yoneda, M., Takatsuki, K., Oiso, Y., Takano, T., Kurokawa, M., Ota, A., Tomita, A., Ohno, T., Okano, K., Kanazawa, T. Endocrinol. Jpn. (1986) [Pubmed]
  9. Correlation among markers of renal osteodystrophy in pediatric hemodialysis patients. Piscitelli, J., Cabansag, M.R., Silverstein, D.M. Journal of pediatric endocrinology & metabolism : JPEM. (1999) [Pubmed]
  10. Influence of thyroid function on serum bone Gla protein. Yoneda, M., Takatsuki, K., Yamauchi, K., Oiso, Y., Kurokawa, M., Kawakubo, A., Izuchi, K., Tanaka, H., Kozawa, O., Miura, Y. Endocrinol. Jpn. (1988) [Pubmed]
  11. Relationship of glucocorticoid dosage to serum bone Gla-protein concentration in patients with rheumatologic disorders. Kotowicz, M.A., Hall, S., Hunder, G.G., Cedel, S.L., Mann, K.G., Riggs, B.L. Arthritis Rheum. (1990) [Pubmed]
  12. Tests of linkage and/or association of genes for vitamin D receptor, osteocalcin, and parathyroid hormone with bone mineral density. Deng, H.W., Shen, H., Xu, F.H., Deng, H.Y., Conway, T., Zhang, H.T., Recker, R.R. J. Bone Miner. Res. (2002) [Pubmed]
  13. Cloning of the bone Gla protein gene from the teleost fish Sparus aurata. Evidence for overall conservation in gene organization and bone-specific expression from fish to man. Pinto, J.P., Ohresser, M.C., Cancela, M.L. Gene (2001) [Pubmed]
  14. Serum bone gla protein (BGP) and other markers of bone mineral metabolism in postmenopausal osteoporosis. Ismail, F., Epstein, S., Pacifici, R., Droke, D., Thomas, S.B., Avioli, L.V. Calcif. Tissue Int. (1986) [Pubmed]
  15. Lack of association between the HindIII RFLP of the osteocalcin (BGP) gene and bone mineral density (BMD) in healthy pre- and postmenopausal Chinese women. Mo, X.Y., Cao, C.K., Xu, F.H., Liu, M.Y., Li, M.X., Qin, Y.J., Zhou, Q., Zhang, Y.Y., Deng, H.W. J. Bone Miner. Metab. (2004) [Pubmed]
  16. Osteocalcin induces chemotaxis, secretion of matrix proteins, and calcium-mediated intracellular signaling in human osteoclast-like cells. Chenu, C., Colucci, S., Grano, M., Zigrino, P., Barattolo, R., Zambonin, G., Baldini, N., Vergnaud, P., Delmas, P.D., Zallone, A.Z. J. Cell Biol. (1994) [Pubmed]
  17. Monoclonal antibodies to native noncollagenous bone-specific proteins. Stenner, D.D., Romberg, R.W., Tracy, R.P., Katzmann, J.A., Riggs, B.L., Mann, K.G. Proc. Natl. Acad. Sci. U.S.A. (1984) [Pubmed]
  18. Retinoic acid modulation of mRNA levels in malignant, nontransformed, and immortalized osteoblasts. Zhou, H., Hammonds, R.G., Findlay, D.M., Fuller, P.J., Martin, T.J., Ng, K.W. J. Bone Miner. Res. (1991) [Pubmed]
  19. Purification of matrix Gla protein from a marine teleost fish, Argyrosomus regius: calcified cartilage and not bone as the primary site of MGP accumulation in fish. Simes, D.C., Williamson, M.K., Ortiz-Delgado, J.B., Viegas, C.S., Price, P.A., Cancela, M.L. J. Bone Miner. Res. (2003) [Pubmed]
  20. Identification of peptide fragments generated by digestion of bovine and human osteocalcin with the lysosomal proteinases cathepsin B, D, L, H, and S. Baumgrass, R., Williamson, M.K., Price, P.A. J. Bone Miner. Res. (1997) [Pubmed]
  21. Increased circulating levels of gamma-carboxyglutamic acid-containing protein and decreased bone mass in children on anticonvulsant therapy. Takeshita, N., Seino, Y., Ishida, H., Seino, Y., Tanaka, H., Tsutsumi, C., Ogata, K., Kiyohara, K., Kato, H., Nozawa, M. Calcif. Tissue Int. (1989) [Pubmed]
  22. Serum markers of bone formation in parenteral nutrition patients. Lipkin, E.W., Ott, S.M., Klein, G.L., Deftos, L.J. Calcif. Tissue Int. (1990) [Pubmed]
  23. Serum osteocalcin and calcitropic hormones in a homogeneous group of patients with rheumatoid arthritis: its implication in the osteopenia of the disease. Rico, H., Revilla, M., Alvarez de Buergo, M., Villa, L.F. Clinical and experimental rheumatology. (1993) [Pubmed]
  24. Changes in bone and calcium metabolism following hip fracture in elderly patients. Sato, Y., Kaji, M., Higuchi, F., Yanagida, I., Oishi, K., Oizumi, K. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. (2001) [Pubmed]
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