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

• Osteoblasts from both stromal and calvarial explants showed delayed maturation in vitro as measured by expression of alkaline phosphatase (ALP), induction of mRNA encoding osteocalcin and mineral deposition [7].
• Increased bone formation in osteocalcin-deficient mice [8].
• Increased bone formation and decreased osteocalcin expression induced by reduced Twist dosage in Saethre-Chotzen syndrome [9].
• Reduced bone density is accompanied by increased activity of osteoclasts and upregulation of genes that are related to osteoblast differentiation, including osteopontin, osteonectin, and osteocalcin [10].
• To test this hypothesis, we administered prednisolone to 7-mo-old mice for 27 d and found decreased bone density, serum osteocalcin, and cancellous bone area along with trabecular narrowing [11].

Chemical compound and disease context of Bglap1

• The Ad-OC-TK virus plus ACV treatment appears to be highly selective in blocking the growth of both murine and human osteosarcoma cell lines in vitro and murine osteosarcoma in vivo [12].
• The fully differentiated rat osteoblast-like osteosarcoma 17/2.8 cells responded rapidly to melatonin and displayed an increase in the expression of BSP, ALP, and osteocalcin genes within 1 h of exposure to the hormone [13].
• NET at picomolar concentrations in vitro stimulated the proliferation of human TE85 osteosarcoma cells as assessed by the increase in [3H]thymidine incorporation into DNA and in cell number and also stimulated the release of osteocalcin in both the presence and absence of 10 nM 1,25-(OH)2D3 [14].
• To simultaneously assess bone resorption and bone formation in inflammatory arthritis, we developed a histological technique that allows visualization of osteoblast function by in-situ hybridization for osteocalcin and osteoclast function by histochemistry for tartrate-resistant acid phosphatase [15].

Biological context of Bglap1

• These data demonstrate the crucial role of Osf2 in controlling osteocalcin gene expression [16].
• The mouse osteocalcin gene cluster contains three genes with two separate spatial and temporal patterns of expression [17].
• From sequence inspection, DNA transfection experiments, and DNA binding assays, we could not identify a functional vitamin D-responsive element in the promoter of OG2 or in the first 3.3 kilobases of the OG1 promoter [18].
• MINT, the Msx2 interacting nuclear matrix target, enhances Runx2-dependent activation of the osteocalcin fibroblast growth factor response element [19].
• To define the mechanisms of osteocalcin cell-specific gene expression in vivo, we generated transgenic mice harboring deletion mutants of the promoter region of OG2, one of the mouse osteocalcin genes [16].

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

• Chromatin immunoprecipitation assays revealed a molecular switch in HD protein association with the bone-specific osteocalcin (OC) gene [30].
• Transcription factor binding to the OC negative GRE was studied by electrophoretic mobility shift assays [25].
• Northern hybridization analysis revealed more mRNA for collagen type I (2-fold) and 50% more for OC at 14 days and 21 days, whereas OPN and Cbfa1 mRNA expression remained unaffected by the medium perfusion [31].
• Western and northern blot analyses suggest that TLE expression is regulated reciprocally with the levels of OC gene expression during osteoblast differentiation [32].
• Osteogenesis, as determined by the expression of Cbfa1 and osteocalcin (OC) messenger RNAs (mRNAs), was induced strongly in C3H10T1/2 cells cocultured with both chondrocyte cell populations but was not induced by coculture with either osteoblasts or skin fibroblasts [33].

References