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)

The nervous system may play a role in regulation of bone metabolism. The effects of norepinephrine(NE), vasoactive intestinal peptide(VIP), and ATP on cytosolic Ca2+ were assessed in a rat osteoblast-like osteosarcoma cell line (UMR-106) responsive to PTH. All three transmitters transiently increased Ca2+, with ATP much greater than PTH greater than NE = VIP, and then caused sustained increases in Ca2+. The ATP-induced transient resulted from mobilization of intracellular Ca2+ store, while NE and VIP-induced transients also involved influx of Ca2+. Later sustained increases by all agonists were dependent upon extracellular Ca2+. Release of intracellular Ca2+ by ATP was associated with a marked increase in IP3 but without a significant change in cAMP. NE, VIP, and ATP, through regulation of Ca2+ metabolism, may be involved in various osteoporotic conditions.
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PMID:Neurotransmitter regulation of cytosolic calcium in osteoblast-like bone cells. 255 24

Human PTH-related protein (hPTHrP) has been characterized as a product of tumor cells with sequence homology to the biologically active amino-terminal portion of human PTH (hPTH). We measured the relative activities of synthetic amino-terminal sequences of hPTH-(1-34) and hPTHrP-(1-34) to stimulate production of cAMP in intact human SaOS-2 osteosarcoma cells. Both peptides enhanced cAMP production at concentrations of 2.5-7.5 X 10(-10) M, had parallel dose-response curves, and were of essentially equal potency. Preincubation of SaOS-2 cells with hPTH-(1-34) or hPTHrP-(1-34) for 1 or 4 h induced homologous desensitization to a second challenge with the same peptide as well as heterologous desensitization to the other PTH peptide, but had little or no effect on the action of vasoactive intestinal peptide; the magnitudes of homologous and heterologous desensitization induced by the same doses of hPTHrP-(1-34) or hPTH-(1-34) were similar. Bone resorption-stimulating activity was measured using 40Ca2+ release from neonatal mouse calvariae in organ culture after 72 h of incubation. hPTHrP-(1-34) gave a dose-response between 0.2 and 5 ng/ml (5 X 10(-11) and 1.2 X 10(-9) M), was about 3 times more potent than Lilly bovine PTH standard (assuming a SA of 3000 U/mg; 100 U/ml), gave the same maximum response as hPTH-(1-34), and was 20-30% as potent as hPTH-(1-34). Neither hPTH-(1-34) nor hPTHrP-(1-34) enhanced prostaglandin production in mouse calvariae, and indomethacin did not inhibit the bone resorption-stimulating activities of either peptide. We conclude that hPTHrP-(1-34) and hPTH-(1-34) have similar high specific biological activities to stimulate production of cAMP in human osteoblast-like cells, but that hPTHrP-(1-34) is modestly less potent than hPTH-(1-34) to stimulate bone resorption in mouse calvariae.
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PMID:Human parathyroid hormone (PTH)-related protein and human PTH: comparative biological activities on human bone cells and bone resorption. 284 88

We have investigated the actions of 17 beta-estradiol (E2) on the production of cAMP stimulated by synthetic human PTH [hPTH-(1-34)], synthetic hPTH-related protein [hPTHrP-(1-34)], and vasoactive intestinal peptide (VIP) in human (SaOS-2) and rat (ROS 17/2.8) osteoblast-like osteosarcoma cells. In SaOS-2 cells, hPTH-(1-34) (2.5 nM), hPTHrP-(1-34) (2.5 nM), and VIP (10-100 nM) stimulated the accumulation of cAMP markedly (greater than 20- to 30-fold in 1 h). Cells were preincubated in serum-free medium for 4-24 h, then in the absence or presence of E2 for 4 h before a 1-h stimulation with peptide hormone in the absence of E2. In SaOS-2 cells, pretreatment with E2 (10(-12)-10(-8) M) for 4 h inhibited by up to 50% the accumulation of cAMP stimulated by hPTH-(1-34) or hPTHrP-(1-34), but E2 had no inhibitory effect on VIP action. 17 alpha-Estradiol had no inhibitory action on hPTH- or hPTHrP-stimulated accumulation of cAMP at concentrations as high as 10(-8) M. Additional evidence against a nonspecific effect of E2 was the total lack of inhibition of cAMP accumulation stimulated by hPTH-(1-34) or hPTHrP-(1-34) in ROS 17/2.8 cells at concentrations of E2 up to 10(-6) M. We conclude that E2 can act directly and rapidly in human osteoblast-like cells to modulate selectively the ability of hPTH and hPTHrP to enhance the production of cAMP.
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PMID:Direct modulation by estradiol of the response of human bone cells (SaOS-2) to human parathyroid hormone (PTH) and PTH-related protein. 290 73

Influx of extracellular Ca++ into bone cells has been postulated as an early action of PTH and other bone resorption-stimulating factors. To test this hypothesis directly, we measured the cytosolic free Ca2+ concentration ([Ca2+]i) in two hormone-responsive human (SaOS-2 and G-292) and two rat osteosarcoma cell lines (Ros 25/1 and Ros 17/2.8) and in primary cultures of bone cells from neonatal mouse calvaria using the fluorescent Ca2+ indicator Quin 2. Actions of bovine PTH-(1-34), vasoactive intestinal peptide, epidermal growth factor, prostaglandin E2, and ionomycin were studied. Medium cAMP (20 min; 37 C; 25 microM 3-isobutyl-1-methylxanthine) was quantitated by RIA. Basal [Ca2+]i was: SaOS-2, 126 +/- 8 nM; G-292, 61 +/- 6 nM; Ros 25/1, 109 +/- 15 nM; Ros 17/2.8, 363 +/- 42 nM; and primary cultures, 266 +/- 39 nM (mean +/- SE; n = 3-14). In each cell type, no acute (1 sec to 20 min) spike in [Ca2+]i was observed in response to PTH (24-120 nM), vasoactive intestinal peptide (100 nM), epidermal growth factor (17 nM), or prostaglandin E2 (2.8 microM). However, in SaOS-2 cells only, PTH reproducibly increased [Ca2+]i 10-15% above basal values beginning about 3 min after hormone addition, and this small increase returned to baseline at 15-20 min. Ionomycin (100 nM) elicited an immediate spike in [Ca2+]i to levels 2- to 4-fold above basal in all cells; the peak [Ca2+]i decayed rapidly (within 4-5 min) to baseline in G-292, Ros 25/1, and Ros 17/2.8 cells. The decay of peak [Ca2+]i in SaOS-2 was prolonged. To test for intact hormone responses in Quin 2-loaded cells, cAMP accumulation was measured. In SaOS-2 and Ros 17/2.8, both control and Quin 2-loaded cells showed similar increases in cAMP in response to PTH. Considering the limitations of the Quin 2 technique, we conclude that in the four hormone-responsive bone cell lines and primary cultures of bone cells tested, acute elevation of [Ca2+]i is not an inevitable consequence of receptor occupancy and/or adenylate cyclase activation by bone resorption-stimulating hormones.
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PMID:Measurement of cytosolic free Ca2+ concentrations in human and rat osteosarcoma cells: actions of bone resorption-stimulating hormones. 300 4

We have previously reported that vasoactive intestinal peptide (VIP) stimulates bone resorption in organ culture via a cAMP-dependent mechanism. Here we describe functional receptors for VIP on a clonal line of human osteosarcoma cells, SaOs-2. SaOs-2 cells respond to VIP with an increase in cAMP. The effect was rapid (2 min) and dose dependent from 0.15-15 nM VIP, with half-maximal stimulation at 1.4 nM. SaOs-2 cells produce prostaglandin E2 (PGE2) and respond to exogenous PGE2 with increases in cAMP approximately one third as great as those induced by VIP. However, the VIP-stimulated increases in cAMP occurred without detectable increases in PGE2 production, and increases in cAMP were unaffected by the cyclooxygenase inhibitor indomethacin. SaOs-2 cells pretreated with VIP for 24 h were significantly less responsive to a second acute challenge with VIP, but retained their ability to respond to PGE2. Similarly, pretreatment with PGE2 induced homologous desensitization to PGE2, but had no effect on the VIP-stimulated increase in cAMP. These patterns of response paralleled those previously described in whole bone in organ culture. Binding studies with [125I]VIP demonstrated specific, saturable, high affinity receptors for VIP on SaOs-2 cells. Scatchard analysis of [125I]VIP binding at 37 C resulted in a curvilinear plot. Analysis based upon the assumption of two independent binding sites gave Kd values of 0.44 and 17 nM for high and low affinity binding sites, respectively. The numbers of high and low affinity sites per cell were determined to be 8,500 and 57,000, respectively. Binding of [125I]VIP was partially inhibited by two related peptides, secretin and PHI-27, but not by PTH, calcitonin or a variety of unrelated peptides. We conclude that the action of VIP on human SaOs-2 cells is similar to that observed in intact mouse calvaria, and that these cells provide a good model for the study of the initial steps of VIP action in bone.
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PMID:Functional receptors for vasoactive intestinal peptide on human osteosarcoma cells. 632 42