Osteocalcin: Genetic and Physical Mapping of the Human Gene BGLAP and Its Potential Role in Postmenopausal Osteoporosis

Raymond, Michael H.; Schutte, Brian C.; Torner, James C.; Burns, Trudy L.; Willing, Marcia

doi:10.1006/geno.1999.5893

Cited by 42 publications

(36 citation statements)

References 43 publications

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“…This is followed by allele 7 (20.6%), 4 (15.8%), 5 (12.0%), 3 (10.0%), 6 (6.2%) and 13 (5.7%). Major allelic frequencies are similar to those previously reported [4].…”

Section: Study Populationsupporting

confidence: 78%

“…Amplification products were pooled, precipitated, combined with loading buffer, formamide and an internal size standard (GS400HD, PE Biosystems), then size-separated and detected using ABI PrismTM 377 automated sequencers (PE Biosystems). The D1S3737 alleles were sized, identified and coded using methods previously described [13] and were re-coded to correspond with published alleles [4]. Alleles not previously described were designated new codes.…”

Section: Measurementsmentioning

confidence: 99%

“…The human osteocalcin gene, also referred to as BGLAP (bone gamma-carboxyglutamate (gla) protein), has been mapped to the long arm of chromosome 1 (1q21-1q23) [4]. It has four exons and codes for a polypeptide consisting of a 23 amino acid signal peptide, a 26 amino acid propeptide and a mature protein of 49 amino acids.…”

Section: Introductionmentioning

confidence: 99%

“…We therefore consider the osteocalcin gene to be an excellent candidate to study association with osteoporosis and fractures. The D1S3737 marker used for this study is estimated to be between 50kb (http://genome.ucsc.edu) and 180kb [4] from the BGLAP gene.…”

Section: Introductionmentioning

confidence: 99%

“…To test for the gene's possible role in osteoporosis, we genotyped 1366 non-identical (dizygotic or DZ) female twins for the microsatellite marker D1S3737, previously reported to be linked to the osteocalcin gene and associated with BMD at the left hip femoral neck [4]. DZ twins offer the advantages of being matched for age and that family data can be used to test and control for potential confounding due to population stratification and admixture.…”

Section: Introductionmentioning

confidence: 99%

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Linkage and Association for Bone Mineral Density and Heel Ultrasound Measurements with a Simple Tandem Repeat Polymorphism near the Osteocalcin Gene in Female Dizygotic Twins

et al. 2002

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In this confirmatory candidate gene study, we investigated possible linkage and association for bone density, heel ultrasound and bone turnover with the osteocalcin gene using the nearby (50-180kb) microsatellite marker D1S3737. Non-identical twin sisters aged 18-75 years at first interview were recruited for the study from the St Thomas' UK Adult Twin Registry with 1366 women being genotyped for marker D1S3737. Linkage, allelic association and joint linkage and association tests were carried out using quantitative transmission disequilibrium tests (QTDT), along with post-hoc multivariate tests of linkage and association. Phenotypes tested were bone mineral density (BMD) at the spine, left forearm and left total hip; quantitative ultrasound measurements of the heel including velocity of ultrasound (VOS) and broadband ultrasound attenuation (BUA); and bone turnover markers, urine deoxypyridinoline (DPD), serum osteocalcin, bone specific and total alkaline phosphatase (ALP). BMD and ultrasound variables showed evidence of pleiotropic linkage ( p = 0.05) and association ( p = 0.02) with the marker in postmenopausal women. Bone markers showed little or no evidence of linkage and association for any age group. Evidence for pleiotropic linkage appeared to be strongest for BUA and spine BMD in postmenopausal women. The univariate test statistic for BUA was chi(2)(1)=12.8 ( p = 0.0003), equivalent to a LOD score of 2.8. DPD showed borderline evidence of linkage to the marker for women of all ages. Multivariate model-fitting showed allele 10 to be negatively associated with BMD, VOS and BUA via a common pathway, suggesting the putative functional polymorphism affects both bone content and structure through shared underlying metabolic pathways. It is likely that the alleles are in linkage disequilibrium with functional polymorphism(s) in or nearby the osteocalcin gene, which may contribute to the onset of osteoporosis.

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“…This is followed by allele 7 (20.6%), 4 (15.8%), 5 (12.0%), 3 (10.0%), 6 (6.2%) and 13 (5.7%). Major allelic frequencies are similar to those previously reported [4].…”

Section: Study Populationsupporting

confidence: 78%

Section: Measurementsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Linkage and Association for Bone Mineral Density and Heel Ultrasound Measurements with a Simple Tandem Repeat Polymorphism near the Osteocalcin Gene in Female Dizygotic Twins

et al. 2002

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Effects of physiological mechanical strains on the release of growth factors and the expression of differentiation marker genes in human osteoblasts growing on Ti‐6Al‐4V

Kokkinos

Zarkadis

Kletsas

et al. 2008

J Biomedical Materials Res

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Mechanical loading factors at the bone-implant interface are critical for the osseointegration and clinical success of the implant. The aim of the present investigation was to study the effects of mechanical strain on the orthopedic biomaterial Ti-6Al-4V/osteoblast interface, using an in vitro model. Homogeneous strain was applied to human bone marrow derived osteoblasts (HBMDOs) cultured on Ti-6Al-4V, at physiological levels (strain magnitudes 500 microstrain (microepsilon) and 1000 microepsilon, at frequencies of load application 0.5 Hz and 1 Hz), by a mechanostimulatory system, based on the principle of four-point bending. Semi-quantitative reverse transcription-polymerase chain reaction (sqRT-PCR) was used to determine the mRNA expression of Cbfa1 and osteocalcin at different loading conditions. The release of growth factors as a response to stretch was also investigated by transferring stretch-conditioned media to nonstretched cells and by measuring their effect on the regulation of DNA synthesis. Mechanical loading was found to contribute to the regulation of osteoblast differentiation by influencing the level of the osteoblast-specific transcription factor Cbfa1, both at the mRNA and protein level, and also the level of osteocalcin, which is regarded as the most osteoblast-specific gene. Both genes were differentially expressed shortly after the application of different mechanical stimuli, in terms of strain frequency, magnitude, and time interval. Media conditioned from mechanically stressed HBMDOs stimulate DNA synthesis more intensely compared to media conditioned from unstressed control cultures, indicating that mechanical strain induces the release of a mitogenic potential that regulates cell proliferation.

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Potential of chemically modified hydrophilic surface characteristics to support tissue integration of titanium dental implants

et al. 2008

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In the past, several modifications of specific surface properties such as topography, structure, chemistry, surface charge, and wettability have been investigated to predictably improve the osseointegration of titanium implants. The aim of the present review was to evaluate, based on the currently available evidence, the impact of hydrophilic surface modifications of titanium for dental implants. A surface treatment was performed to produce hydroxylated/hydrated titanium surfaces with identical microstructure to either acid-etched, or sand-blasted, large grit and acid-etched substrates, but with hydrophilic character. Preliminary in vitro studies have indicated that the specific properties noted for hydrophilic titanium surfaces have a significant influence on cell differentiation and growth factor production. Animal experiments have pointed out that hydrophilic surfaces improve early stages of soft tissue and hard tissue integration of either nonsubmerged or submerged titanium implants. This data was also corroborated by the results from preliminary clinical studies. In conclusion, the present review has pointed to a potential of hydrophilic surface modifications to support tissue integration of titanium dental implants.

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Osteocalcin: Genetic and Physical Mapping of the Human Gene BGLAP and Its Potential Role in Postmenopausal Osteoporosis

Cited by 42 publications

References 43 publications

Linkage and Association for Bone Mineral Density and Heel Ultrasound Measurements with a Simple Tandem Repeat Polymorphism near the Osteocalcin Gene in Female Dizygotic Twins

Linkage and Association for Bone Mineral Density and Heel Ultrasound Measurements with a Simple Tandem Repeat Polymorphism near the Osteocalcin Gene in Female Dizygotic Twins

Effects of physiological mechanical strains on the release of growth factors and the expression of differentiation marker genes in human osteoblasts growing on Ti‐6Al‐4V

Potential of chemically modified hydrophilic surface characteristics to support tissue integration of titanium dental implants

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