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

• It appears that at present, serum BGP is the one bone protein that has the most promise for assisting in the diagnosis and management of high turnover metabolic bone disease states [4].
• In addition, the data may also explain the observation that bone Gla protein is more sensitive to warfarin than the coagulation proteins [5].
• When BGP concentrations were added to the models, the significance of estrogen was reduced, suggesting that a portion of the estrogen effect was mediated through effects on rates of bone remodelling [6].
• After parathyroidectomy, sBGP slowly returned to normal values within 2-6 mo, suggesting that sBGP reflects increased bone turnover rather than a direct effect of parathyroid hormone on BGP synthesis at the cell level [7].
• Serum bone gamma carboxyglutamic acid-containing protein in primary hyperparathyroidism and in malignant hypercalcemia. Comparison with bone histomorphometry [7].

Chemical compound and disease context of BGLAP

• Assessment of cadmium-induced osteopenia by measurement of serum bone Gla protein, parathyroid hormone, and 1 alpha,25-dihydroxyvitamin D [3].
• The serum bone Gla-protein (BGP) and urinary gamma-carboxyglutamic acid (gamma-Gla) levels were determined in patients with primary hyperparathyroidism (PHP) [8].
• We measured serum PTH, AP, Ca2+, and BGP levels in a group (n=23) of pediatric patients with ESRD and assessed the correlation among the markers [9].
• In the patients with hypothyroidism, serum BGP increased significantly in parallel with increases in serum free triiodothyronine with thyroxine therapy [10].
• Serum bone Gla-protein (BGP) measurements in 50 rheumatic disease patients receiving long-term prednisone therapy revealed an inverse relationship (r = -0.71, P less than 0.001) between serum BGP levels and prednisone dosage [11].

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

• Osteocalcin, also called Bone Gla Protein (BGP), is the most abundant of the non-collagenous proteins of bone produced by osteoblasts [16].
• The action of BGP on osteoclasts was mediated by an intracellular calcium increase due to release from thapsigargin-sensitive stores [16].
• Hybridoma technology was used for preparation of murine monoclonal antibodies of high titer against bone-Gla protein and osteonectin [17].
• None of the cell lines expressed measurable mRNA for bone gla protein or bone proteoglycan II [18].
• In mineralized tissues, the MGP gene was predominantly expressed in cartilage from branchial arches, with no expression detected in the different types of bone analyzed, whereas BGP mRNA was located in bone tissue as expected [19].

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].

References