UMLS:C0029463 - FACTA Search

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Query: UMLS:C0029463 (osteosarcoma)
16,637 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Prostaglandin E2 (PGE2), PTH, and epidermal growth factor (EGF) are potent regulators of osteoblast proliferation. In UMR 106-01 rat osteosarcoma cells with osteoblast-like features, PGE2 and PTH inhibit, while EGF stimulates, mitogenesis. Both PGE2 and PTH increase intracellular cAMP levels, cytosolic calcium, and inositol phosphate turnover. In a variety of cell types, EGF mediates its effects in part via activation of receptor protein-tyrosine kinase and other protein kinases, such as protein kinase-C. The nuclear mechanisms of PGE2, PTH, and EGF regulation of osteoblast proliferation are unknown. Accordingly, we have examined the effects of these agents on mitogenesis, second messenger generation, and primary response genes, which may link second messenger activation to subsequent alterations in gene expression. Northern blot analysis of mRNA from UMR 106-01 cells treated for 3 h with 2 microM PGE2, 10 nM PTH, or 10 ng/ml EGF in the presence of cycloheximide demonstrated that all three agents induced the expression of c-fos and c-jun mRNA. In contrast, only EGF stimulated cellular proliferation and induced Egr-1 mRNA. Also, unlike PGE2 and PTH, EGF did not increase intracellular cAMP levels. c-fos mRNA was induced by treatment with 50 ng/ml tetradecanoyl phorbol acetate or by 40 ng/ml forskolin, while induction of Egr-1 mRNA was stimulated by treatment with tetradecanoyl phorbol acetate, but not forskolin. Thus, EGF signal transduction differs from that of PGE2 and PTH in UMR 106-01 osteoblast-like cells, in that EGF does not stimulate the protein kinase-A second messenger system, but causes activation of Egr-1, a primary response gene that may play a role in the mitogenic effect of EGF.
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PMID:The effects of prostaglandin E2, parathyroid hormone, and epidermal growth factor on mitogenesis, signaling, and primary response genes in UMR 106-01 osteoblast-like cells. 133 Apr 91

It is evident from the present analysis that although a role for Ca2+ in controlling hypertonic cell volume regulation and RVI mechanisms has not been shown, Ca2+ plays a central role in activating and controlling hypotonic cell volume regulation and RVD mechanisms in most cells. However, this Ca2+ dependency is highly variable among cell types and tissues. Cells can be grouped into three general categories based on the relative dependency of RVD on Ca2+: 1) cells that are highly dependent on extracellular Ca2+ and the activation of Ca2+ influx, supposedly reflecting activation of Ca2+ channels, such as observed for the renal PST cells and osteosarcoma cells; 2) cells that are not dependent on extracellular Ca2+ and Ca2+ influx but that require at least a certain basal intracellular Ca2+ level or transient release of Ca2+ from internal stores, such as observed for the Ehrlich ascites tumor cells and medullary thick ascending limb cells; and 3) cells that display little if any Ca2+ dependency, such as the lymphocytes. There is initial evidence that this variable dependency of RVD on Ca2+ may reflect, in large part, a variable Ca2+ threshold of RVD processes, although this notion has not been fully investigated. The site and mechanism of Ca2+ dependency of RVD are poorly understood. Initial studies pointed to a possible direct control of K+ and/or Cl- channels by Ca2+ to modulate KCl efflux and, hence, RVD. This view appears to be too simplistic, however, as it is increasingly evident that the ion channels involved in RVD may not be directly Ca2+ dependent and that some other regulatory process controlling the channels, perhaps a phosphorylation step, may be the Ca(2+)-dependent event. Given the added complexity of the time-dependent variability of the action of Ca2+, i.e., the Ca2+ window, coupled with the variability of the RVD mechanisms among cell and tissue types, it is likely that the RVD mechanism is a highly complex process involving events and biochemical pathways throughout the cell rather than events simply localized to the inner face of the plasma membrane. It remains for future studies to determine the exact biochemical events that underly the RVD mechanism and its control, and the Ca2+ dependency of each step, before a full understanding will be attained of the role of Ca2+ in modulating RVD.
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PMID:Calcium signaling in cell volume regulation. 133 89

UMR 106 rat osteogenic sarcoma cells were studied with the whole cell patch clamp technique to investigate the presence of voltage-gated inward currents. In barium (Ba2+)-containing medium, depolarizing jumps revealed both transient (T-type) and sustained (L-type) Ba2+ currents. The L-type component was dihydropyridine-sensitive: the agonist Bay K 8644 increased the amplitude of the L-type Ba2+ current. A new dihydropyridine calcium channel blocker, S 11568 ((+/-)-2(2-[2-(aminoethoxy)ethoxyl]methyl)4-(2',3'- dichlorophenyl)3-ethoxycarbonyl-5-methoxycarbonyl-6-methyl-1,4- dihydropyridine, and its enantiomers, S 12967 ((+)-S 11568) and S 12968 ((-)-S 11568), inhibited the L-type Ba2+ current. IC50 values at a holding potential (VH) of -50 mV were 90 nM for S 11568, 800 nM for S 12967 and 45 nM for S 12968. At VH = -80 mV, S 12968 was less potent (IC50 near 500 nM). In contrast, S 12968 was without appreciable effect on the T-type component of the inward current through Ca2+ channels. Our results indicate that UMR 106 cells express both T-type and L-type Ca2+ channels and could be used to study the modulation by Ca2+ channel blocking agents, such as S 12968, of the hormonal regulation of Ca2+ fluxes across the osteoblast membrane.
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PMID:Ca2+ channel inhibition in a rat osteoblast-like cell line, UMR 106, by a new dihydropyridine derivative, S11568. 138 78

We have previously shown that one of the rapid nongenomic actions of 1 alpha,25-dihydroxyvitamin D3 (1 alpha,25-(OH)2D3), the increase in intracellular calcium (Ca2+), accompanies the increased osteocalcin (OC) mRNA steady-state levels in rat osteosarcoma cells. To determine the functional significance of the nongenomic actions, we have measured changes in intracellular Ca2+ as an indicator of the rapid effects and have assessed the effect of inhibition of the rapid increase in cellular Ca2+ by the inactive epimer, 1 beta, 25-dihydroxyvitamin D3 (1 beta,25-(OH)2D3), on OC mRNA steady-state levels and transcription. 1 beta,25-dihydroxyvitamin D3 inhibited 1 alpha,25-(OH)2D3 induced increases in intracellular Ca2+ and OC mRNA transcription at 1 hr and OC mRNA steady state levels at 3 hr. 1 beta,25-Dihydroxyvitamin D3 did not alter the binding of the vitamin D receptor complex to the vitamin D responsive element of the OC gene. The results demonstrate the functional importance of the rapid, nongenomic actions of 1 alpha,25-(OH)2D3 in the genomic activation of the OC gene by the hormone in rat osteoblast-like cells, perhaps by modifying subtle structural and/or functional properties of the vitamin D-receptor DNA complex or by affecting other protein DNA interactions that support OC gene transcription.
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PMID:The rapid nongenomic actions of 1 alpha,25-dihydroxyvitamin D3 modulate the hormone-induced increments in osteocalcin gene transcription in osteoblast-like cells. 142 79

In a previous study, osteosarcoma cells expressing both 5-lipoxygenase (5-LO) and 5 lipoxygenase-activating protein (FLAP) synthesized leukotrienes upon A23187 stimulation (Dixon, R. A. F., R. E. Diehl, E. Opas, E. Rands, P. J. Vickers, J. F. Evans, J. W. Gillard, and D. K. Miller. 1990. Nature (Lond.). 343:282-284). Osteosarcoma cells expressing 5-LO but not expressing FLAP were unable to synthesize leukotrienes. Thus, it was determined that FLAP was required for the cellular synthesis of leukotrienes. To examine the role of FLAP in A23187-induced translocation of 5-LO to a membrane fraction, we have studied the A23187-stimulated translocation of 5-LO in osteosarcoma cells expressing both 5-LO and FLAP, and in osteosarcoma cells expressing 5-LO only. We demonstrate that in cells expressing both 5-LO and FLAP, 5-LO translocates to membranes in response to A23187 stimulation. This 5-LO translocation is inhibited when cells are stimulated in the presence of MK-886. In osteosarcoma cells expressing 5-LO but not expressing FLAP, 5-LO is able to associate with membranes following A23187 stimulation. In contrast to the cells containing both 5-LO and FLAP, MK-886 is unable to prevent 5-LO membrane association in cells transfected with 5-LO alone. Therefore, we have demonstrated that in this cell system, 5-LO membrane association and activation can be separated into at least two distinct steps: (1) calcium-dependent movement of 5-LO to membranes without product formation, which can occur in the absence of FLAP (membrane association), and (2) activation of 5-LO with product formation, which is FLAP dependent and inhibited by MK-886 (enzyme activation).
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PMID:A23187-induced translocation of 5-lipoxygenase in osteosarcoma cells. 146 57

Using rat calvaria cells in primary culture monolayers and bone-like nodules, and isolated rat osteosarcoma cells, we show via laser scanning confocal microscopy and fluorescent indicator fluo-3/AM, that mechanical perturbation of a cell results in a transient increase (pulse) of measured intracellular calcium concentration that propagates from cell to cell, even between cells connected only by a thin process. The calcium pulse does not occur in the mechanically perturbed cell in calcium-free bathing medium, nor is there pulse propagation under this condition. Halothane, which blocks gap junctions, inhibits propagation. Propagation velocity does not decrease with successive cell to cell steps. These observations suggest the existence of a self-regenerating calcium signaling mechanism that may be based on a form of calcium-induced calcium release.
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PMID:Propagation of a calcium pulse between osteoblastic cells. 151 Jun 56

Matrix Gla protein (MGP) is a 14-kDa protein found in bone and cartilage which contains the unusual amino acid gamma-carboxyglutamic acid (Gla). The biological function of this protein has not been elucidated. Here we have demonstrated the adherence of chondrocytes, fibroblasts, osteosarcoma cells, and kidney mesangial cells to MGP purified from bovine bone. Maximum adherence occurred at MGP concentrations of 0.5-1.0 micrograms/ml. Removal of the calcium-binding Gla residues by thermal decarboxylation of MGP destroyed the proteins' cell adherence properties. Cell adherence to MGP was not affected by the presence of antibodies directed against the C-terminal (non-Gla) portion of the protein or the presence of cycloheximide during the adherence assay. However, the Arg-Gly-Asp-containing synthetic peptide Gly-Arg-Gly-Asp-Ser-Pro significantly inhibited cell attachment to MGP, whereas the control peptide Gly-Arg-Gly-Glu-Ser-Pro had minimal effect. These data indicate that MGP may function in mediating cell attachment to the extracellular matrix via a receptor that requires intact Gla residues and that can be inhibited by Arg-Gly-Asp-containing peptides.
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PMID:Cell adhesion to matrix Gla protein and its inhibition by an Arg-Gly-Asp-containing peptide. 157 89

The skeleton is the major reservoir of lead and calcium in humans, and plays an important role in systemic calcium regulation. Lead perturbs normal calcium transport and second messenger function, directly or indirectly, in virtually all cells studies so far. Therefore, we and others have postulated that an early and discrete toxic effect of lead is perturbation of one or more loci within the calcium messenger system. To understand further the role of lead on calcium homeostasis in bone, we undertook this study to characterize calcium homeostasis and the effect of lead on calcium homeostasis in rat osteosarcoma (ROS 17/2.8) cells, which exhibit the osteoblast phenotype. ROS cells were incubated in medium containing 45Ca for 20 hours. Monitoring the efflux of 45Ca from the cultures for 210 minutes allowed for the determination of kinetic parameters defining steady state calcium homeostasis. Three distinct intracellular kinetic calcium pools characterized 45Ca homeostasis. Treatment with either 400 ng parathyroid hormone (PTH)/ml culture medium for 1 hour or 25 microM lead for 20 hours increased total cell calcium. Treatment with PTH caused a larger increase of cell calcium in lead-intoxicated cells than either lead intoxication or PTH treatment alone. This increase suggests that lead may perturb normal calcium-mediated PTH responsiveness of the osteoblast. These experiments further establish a kinetic model for the study of calcium homeostasis in osteoblastic bone cells. The studies also advance the hypothesis that lead-induced perturbations of calcium-mediated processes represent an early effect of lead toxicity at the cellular level.
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PMID:Lead intoxication alters basal and parathyroid hormone-regulated cellular calcium homeostasis in rat osteosarcoma (ROS 17/2.8) cells. 159 81

After demonstrating the presence of matrix vesicles in three osteosarcoma cell lines, MG-63, ROS 17/2.8 and MC-3T3-E1, we sought to determine whether two major enzymes localized to matrix vesicles, alkaline phosphatase and phospholipase A2, could be regulated by 1,25(OH)2D3 and/or TGF beta. Intravesicular calcification is probably dependent on these two enzymes. Alkaline phosphatase is essential for hydrolysis of phosphate-containing substrates and phospholipase A2 hydrolyzes diacylphosphatides in a calcium-mediated manner at lipid-aqueous interfaces leading to changes in membrane fluidity and possibly breakdown of the matrix vesicle. The 1,25(OH)2D3 induced increase of alkaline phosphatase in bone cells is localized to the matrix vesicle. TGF beta also increased alkaline phosphatase activity in two of the cell lines, MG-63 and ROS 17/2.8 but to a greater degree than 1,25(OH)2D3. Matrix vesicle alkaline phosphatase activity exhibited a greater response than that in the plasma membrane. TGF beta increased phospholipase A2 activity in both matrix vesicles and plasma membranes, therefore, no targeting was observed with respect to this enzyme. When TGF beta was combined with 1,25(OH)2D3, 1,25(OH)2D3 had no effect on phospholipase A2 and did not interfere with TGF beta stimulation of phospholipase A2 activity. When 1,25(OH)2D3 and TGF beta were combined, a tremendous synergy was observed in alkaline phosphatase specific activity in both plasma membranes and matrix vesicles with targeting to matrix vesicles. Therefore, TGF beta not only plays an important role in matrix formation and differentiation, but works in conjunction with 1,25(OH)2D3 to greatly potentiate the effects seen with 1,25(OH)2D3 alone.
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PMID:Stimulation of matrix vesicle enzyme activity in osteoblast-like cells by 1,25(OH)2D3 and transforming growth factor beta (TGF beta). 161 Dec 99

Nearly all models of skeleton, cartilage, and dentin mineralization evoke a specific role for matrix vesicles (MV) and alkaline phosphatase (ALP). Nevertheless, the mechanism underlying MV production, mineralization, and the pivotal role of ALP is largely unknown. Previous studies in this laboratory demonstrated that ALP in a human osteosarcoma cell line (SAOS-2) is of the tissue nonspecific ('bone') isoenzyme and lipid-anchored to the plasma membrane in ecto-orientation [1], thus reminiscent of osteoblasts in vivo [2]. Herein, we show that these cells spontaneously release ALP-rich structures (MVs) with the capacity to mineralize. MVs from SAOS-2 cells are 100-200 nm in diameter with characteristic trilaminar membranes. ALP in these vesicles is hydrophobic and lipid-anchored in ecto-orientation in a manner similar to the ALP in the parent SAOS-2 cells. 5'-Nucleotidase, another plasma membrane enzyme, is also abundant in MVs; adenylate cyclase is relatively deficient. Analysis of plasma membrane and MV proteins by 2-D gel electrophoresis reveals many common constituents; nevertheless, MVs contain several unique (or greatly enriched) proteins indicating that SAOS-2 MVs originate from specialized regions of the plasma membrane and are released in the same orientation as the plasma membrane. MVs, unlike plasma membrane vesicles, can cause the formation of insoluble calcium and phosphate in a manner that i) requires ALP substrates; ii) is blocked by ALP inhibition or inactivation; and iii) is not dependent on intact MVs. SAOS-2 derived MVs contain at least 3 protein kinases and their substrates. ALP does not, however, have a major role in regulating the phosphorylation state of these phosphoproteins.
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PMID:Human osteosarcoma cells spontaneously release matrix-vesicle-like structures with the capacity to mineralize. 161

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