Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0029463 (osteosarcoma)
 16,637 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1,25-Dihydroxyvitamin D3 [1,25-(OH)2D3] regulates the synthesis of bone gamma-carboxyglutamic acid (Gla) protein (BGP) by osteoblastic cells. In this study we examined the effect of cAMP, alone and in combination with 1,25-(OH)2D3, on the regulation of BGP mRNA levels in ROS 17/2 rat osteosarcoma cells. Elevation of intracellular cAMP levels by cAMP analogs or by isobutylmethylxanthine (IBMX), forskolin, or PTH, resulted in increased BGP mRNA levels and BGP secretion after 1 day of treatment. The effects of these agents were additive with 1,25-(OH)2D3 in stimulating BGP gene expression. After 4 days of treatment, pertussis toxin (PT) and 1,25-(OH)2D3 were synergistic in stimulating BGP mRNA, and the effect of PT could be mimicked by (Bu)2cAMP, IBMX, forskolin, cholera toxin, and to a lesser extent by PTH. The effect of 1-day treatment with cAMP alone and the synergistic effect with 1,25-(OH)2D3 on the stimulation of BGP mRNA were dependent on cell density, while basal and 1,25-(OH)2D3-stimulated synthesis were not. Cyclic AMP inhibited ROS 17/2 cell growth after 1 day of treatment, an effect that was also dependent on initial cell density. After 4 days of treatment, 1,25-(OH)2D3, cAMP, and PT all demonstrated inhibition of cell growth. When cells were treated with actinomycin D, both 1,25-(OH)2D3 and cAMP stimulation of BGP mRNA were blocked. In addition, neither agent was effective in enhancing BGP mRNA stability when prestimulated cells were exposed to actinomycin D.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Bone Gla protein messenger ribonucleic acid is regulated by both 1,25-dihydroxyvitamin D3 and 3',5'-cyclic adenosine monophosphate in rat osteosarcoma cells. 246 56

The effects of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] on alkaline phosphatase (AP) activity and the synthesis of gamma-carboxy-glutamic acid containing protein (BGP) were compared in phenotypically distinct cloned cell lines derived from the osteoblast-like rat osteogenic sarcoma line ROS 17/2-8. 1,25(OH)2D3 stimulated AP activity and BGP synthesis in phenotypes which exhibited relatively low basal AP activity and high basal BGP levels. In contrast 1,25(OH)2D3 inhibited AP activity in phenotypes that exhibited high basal AP activity. The latter cells had undetectable BGP levels and the synthesis of this protein failed to respond to the 1,25(OH)2D3 stimulus. In the cells that responded to 1,25(OH)2D3 with an increase in AP activity the effect of the hormone on AP could be blocked by actinomycin-D. However in the cells that responded to 1,25(OH)2D3 with inhibition of AP the effect of the hormone on AP was not influenced by actinomycin-D. The directly opposite effects of 1,25(OH)2D3 on the AP activity of the respective clones did not change qualitatively at different stages of culture and could not be accounted by differences in the 1,25(OH)2D3 receptor status nor by different effects of the hormone on cell proliferation. These data raise the possibility that the response of AP to 1,25(OH)2D3 in osteoblastic cells depends on their state of phenotypic differentiation. The stimulatory effect of the hormone in low AP-producing cells might be related to differentiation promoting properties of 1,25(OH)2D3. The inhibitory effect of 1,25(OH)2D3 on AP, unlike the stimulatory effect of the hormone does not appear to be mediated by the classical mechanism of 1,25(OH)2D3 action on the genome and might be associated with dedifferentiated osteoblastic cells.
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PMID:Phenotype-associated changes in the effects of 1,25-dihydroxyvitamin D3 on alkaline phosphatase and bone GLA-protein of rat osteoblastic cells. 348 45

Osteosarcoma cells grown in normal culture medium secrete bone gamma-carboxyglutamic acid protein (BGP, osteocalcin) which is identical with BGP purified from the bone matrix. Two tests indicate that the secreted medium protein contains the full complement of three gamma-carboxyglutamate residues present on BGP purified from the bone matrix. First, the secreted protein from ROS 17/2 and bone matrix BGP have identical isoelectric points (pI = 4.0). Second, they have identical hydroxyapatite binding behavior. If warfarin is added to the culture medium, the secreted protein has a higher isoelectric point (pI = 4.6) and a lower affinity for hydroxyapatite characteristic of thermally decarboxylated or non-gamma-carboxylated BGP. The observed shift in isoelectric point of secreted BGP after warfarin treatment from pH 4.0 to 4.6 is also reflected in the presence of pI = 4.1 and pI = 4.6 species intracellularly. These isoelectric species correspond to fully carboxylated BGP and noncarboxylated BGP, which are in the process of secretion. Addition of 10 micrograms/ml of warfarin causes a specific 47% reduction in secretion rate of BGP, while at the same time, the intracellular BGP concentration increases 3-fold. These phenomena appear related to the interruption by warfarin of the normal sequence of processing of precursor BGP proteins, as a new, immunoreactive species with a higher isoelectric pH not present in control cells appears to be responsible for the increased intracellular antigen within warfarin-treated cells. Our results show that vitamin K-dependent processing is important for normal secretion of BGP from the cell.
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PMID:The vitamin K-dependent bone protein is accumulated within cultured osteosarcoma cells in the presence of the vitamin K antagonist warfarin. 387 73

The molecular cloning of bone gamma-carboxyglutamic acid (Gla) protein (BGP; osteocalcin) was accomplished by constructing a phage lambda gt11 cDNA library from the rat osteosarcoma cell line ROS 17/2 and screening this library with antibodies raised against BGP from rat bone. By sequencing several cloned cDNAs, we have established a 489-base-pair sequence that predicts a mature BGP of 50 amino acid residues with an NH2-terminal extension of 49 residues. The leader peptide consists of a hydrophobic signal peptide followed by a basic propeptide of 26 or 27 residues that is cleaved after an Arg-Arg dipeptide prior to secretion from the cell. Mature rat BGP is extremely homologous to BGPs from other species except for its COOH-terminal sequence. A stretch of 9 residues proximal to the NH2 terminus of secreted BGP is strikingly similar to the corresponding regions in known propeptides of the gamma-carboxyglutamic acid-containing blood coagulation factors. We suggest that this common structural feature may be involved in the posttranslational targeting of these polypeptides for vitamin K-dependent gamma-carboxylation.
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PMID:The propeptide of rat bone gamma-carboxyglutamic acid protein shares homology with other vitamin K-dependent protein precursors. 387 56

We have found that the gamma-carboxyglutamic acid (GLA)-containing protein from bone (BGP, osteocalcin) has chemotactic activity in vitro for a number of cells which are found adjacent to endosteal bone surfaces in vivo. Using the Boyden chamber technique for measuring cell chemotaxis in vitro, we have shown that BGP is chemotactic for cultured human breast cancer cells, human and mouse monocytes, and for cultured rat osteosarcoma cells which have the characteristics of osteoblasts. The migration of these cells in response to BGP is undirectional and not due to spontaneous or random migration. A synthetic peptide (Phe-Tyr-Gly-Pro-Val), which is identical to the carboxy-terminal peptide cleaved from BGP when digested by trypsin, is also chemotactic for the same cells. BGP retains its chemotactic activity after conversion of the gamma-carboxyglutamic acid residues to glutamic acid, indicating that this biological effect requires neither gamma-carboxyglutamate nor the ability of BGP to bind calcium. Since BGP is released from bone during states of increased bone turnover, it is possible that this chemotactic effect of the protein may be a mechanism for recruitment of these cells to sites of active bone remodeling.
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PMID:Chemotactic activity of the gamma-carboxyglutamic acid containing protein in bone. 660 77

Four clonal cell lines derived from a rat osteosarcoma were tested for the ability to secrete the gamma-carboxyglutamic acid-containing protein of bone (BGP) using a specific radioimmunoassay for this protein. Two cell lines secreted BGP into culture media while the other two did not. Other investigators have shown that these two cell lines are also the only ones with the high parathyroid hormone responsiveness and alkaline phosphatase activity expected for osteoblast cells in culture. Both cell lines also form a mineralized sarcoma when implanted in rats. The BGP in culture media is identical in molecular weight and in electrophoretic mobility with the 5800-dalton BGP purified from rat bone. Thus, BGP is probably secreted by osteosarcoma cells directly and not derived from an extracellular precursor by proteolytic cleavage. There are two immunoreactive components within osteosarcoma cells which secrete BGP. One component is identical in molecular weight and electrophoretic mobility with BGP from rat bone. The other component has a higher molecular mass (approximately 9000 daltons) and about half the electrophoretic mobility of BGP from bone. The presence of both components within these cells raises the possibility that the larger component may be an intracellular precursor which is processed to BGP prior to secretion.
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PMID:Secretion of the vitamin K-dependent protein of bone by rat osteosarcoma cells. Evidence for an intracellular precursor. 696 67

Rat osteosarcoma cells respond to 1,25-dihydroxyvitamin D3 with a 6-fold increase in intracellular and secreted levels of the vitamin K-dependent protein of bone (BGP). The rise in intracellular BGP levels is half-maximal at 6.6 h and precedes the rise in medium BGP levels by 6 h, a time course which is consistent with the postulated steroid hormone action of 1,25-dihydroxyvitamin D3. This effect is achieved by physiological levels of 1,25-dihydroxyvitamin D3, with half of the maximal response at a vitamin concentration of 0.04 ng/ml. The specificity of this effect for BGP is demonstrated by the absence of a 1,25-dihydroxyvitamin D3 effect on total protein synthesis by these cells. To our knowledge, BGP is the first example of a bone protein whose rate of synthesis is dramatically and specifically increased by physiological levels of 1,25-dihydroxyvitamin D3. The possible functions of BGP in the biological actions of 1,25-dihydroxyvitamin D3 on bone are discussed.
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PMID:1,25-Dihydroxyvitamin D3 increases synthesis of the vitamin K-dependent bone protein by osteosarcoma cells. 696 60

Silk fibroin (SF)/nano-hydroxyapatite (n-HA) composites are potential biomaterials for bone defect repair. Up to now, the biological evaluation studies of SF/n-HA composites have primarily concentrated on their biocompatibility at cell level such as cell viability and proliferation and tissue level such as material absorption and new bone formation. In this work, SF/n-HA composites were fabricated using a simplified coprecipitation methods and were deposited onto Ti alloy substrates. Then the cell adhesion ability of SF/n-HA composites was observed by SEM and cell proliferation ability of SF/n-HA composites was determined by MTT assay. The ALP activity, BGP contents, and Col I contents of MG-63 human osteosarcoma cells on SF/n-HA composites were quantitatively analyzed. HA nanocrystals were used as controls. These experiments showed that SF/n-HA composites had better cell adhesion and osteogenic differentiation abilities than n-HA materials. This work provides quantitative data to analyze the effect of SF/n-HA composites on cell osteogenic differentiation.
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PMID:Quantitative analyses of the effect of silk fibroin/nano-hydroxyapatite composites on osteogenic differentiation of MG-63 human osteosarcoma cells. 2545 62