Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0265264 (HOS)
 1,119 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hydroxyapatite (HA) is a bioactive dental implant material which accelerates bone formation on its surface. The mechanism of this acceleration is not clear. The elucidation of the cell adhesion might be the key to the understanding of the bioactive mechanism of HA. In this study, we analyzed the adhesion of HOS human osteoblasts onto HA and titanium to find the particular adhesion to HA. In short-term cultures in fetal bovine serum-pre-coated materials, a significantly higher number of cells adhered to HA than to titanium. In addition, serum-free conditions with phosphate-buffered saline pre-coating or bovine serum albumin pre-coating materials were tested. The results were nearly the same among all pre-coating conditions, suggesting that the quantity of cell adhesion was not affected by serum components. However, in the morphological observations by SEM, the form of adhesion was found to differ among pre-coating conditions. The osteoblasts tightly adhered and spread onto both HA and titanium with serum pre-coating, whereas the cells loosely adhered and did not spread without serum. To evaluate the Arg-Gly-Asp (RGD) sequence-specific adhesion, we used synthetic RGD peptides for a competitive inhibition test. The results showed that RGD peptides remarkably inhibited the tight adhesion and spreading of osteoblasts onto HA, whereas they did not strongly inhibit adhesion and spreading onto titanium. These results demonstrate that the regulation of cell adhesion to HA is different from that to titanium. Our study suggests that the RGD-containing serum proteins might have a major role in regulating the specific adhesion of osteoblasts to HA, and in inducing enhanced cell growth and differentiation.
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PMID:RGD peptides regulate the specific adhesion scheme of osteoblasts to hydroxyapatite but not to titanium. 949 21

To assess the role of naturally occurring basic amino acid substitutions in the V3 loop of human immunodeficiency virus type 1 (HIV-1) subtype E on viral coreceptor usage and cell tropism, we have constructed a panel of chimeric viruses with mutant V3 loops of HIV-1 subtype E in the genetic background of HIV-1LAI. The arginine substitutions naturally occurring at positions 8, 11, and 18 of the V3 loop in an HIV-1 subtype E X4 strain were systematically introduced into that of an R5 strain to generate a series of V3 loop mutant chimera. These chimeric viruses were employed in virus infectivity assays using HOS-CD4 cells expressing either CCR5 or CXCR4, peripheral blood mononuclear cells, T-cell lines, or macrophages. The arginine substitution at position 11 of the V3 loop uniformly caused the loss of infectivity in HOS-CD4-CCR5 cells, indicating that position 11 is critical for utilization of CCR5. CXCR4 usage was conferred by a minimum of two arginine substitutions, regardless of combination, whereas arginine substitutions at position 8 and 11 were required for T-cell line tropism. Nonetheless, macrophage tropism was not conferred by the V3 loop of subtype E R5 strain per se. We found that the specific combinations of amino acid changes in HIV-1 subtype E env V3 loop are critical for determining viral coreceptor usage and cell tropism. However, the ability to infect HOS-CD4 cells through either CXCR4 or CCR5 is not necessarily correlated with T-cell or macrophage tropism, suggesting that cellular tropism is not dictated solely by viral coreceptor utilization.
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PMID:Role of naturally occurring basic amino acid substitutions in the human immunodeficiency virus type 1 subtype E envelope V3 loop on viral coreceptor usage and cell tropism. 1036

The SCF-ROC1 ubiquitin-protein isopeptide ligase (E3) ubiquitin ligase complex targets the ubiquitination and subsequent degradation of protein substrates required for the regulation of cell cycle progression and signal transduction pathways. We have previously shown that ROC1-CUL1 is a core subassembly within the SCF-ROC1 complex, capable of supporting the polymerization of ubiquitin. This report describes that the CUL1 subunit of the bacterially expressed, unmodified ROC1-CUL1 complex is conjugated with Nedd8 at Lys-720 by HeLa cell extracts or by a purified Nedd8 conjugation system (consisting of APP-BP1/Uba3, Ubc12, and Nedd8). This covalent linkage of Nedd8 to CUL1 is both necessary and sufficient to markedly enhance the ability of the ROC1-CUL1 complex to promote ubiquitin polymerization. A mutation of Lys-720 to arginine in CUL1 eliminates the Nedd8 modification, abolishes the activation of the ROC1-CUL1 ubiquitin ligase complex, and significantly reduces the ability of SCF(HOS/beta)(-TRCP)-ROC1 to support the ubiquitination of phosphorylated IkappaBalpha. Thus, although regulation of the SCF-ROC1 action has been previously shown to preside at the level of recognition of a phosphorylated substrate, we demonstrate that Nedd8 is a novel regulator of the efficiency of polyubiquitin chain synthesis and, hence, promotes rapid turnover of protein substrates.
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PMID:Conjugation of Nedd8 to CUL1 enhances the ability of the ROC1-CUL1 complex to promote ubiquitin polymerization. 1092 23

We investigated the effects of bradykinin (BK) on the production of interleukin (IL)-6 and prostaglandin PGE(2), whose molecules are capable of stimulating the development of osteoclasts from their hematopoietic precursors as well as the signal transduction systems involved, in human osteoblasts (SaM-1 cells). BK receptors B1 (B1R) and B2 (B2R) were expressed in SaM-1 and osteosarcoma (SaOS-2, HOS, and MG-63) cells. Treatment of SaM-1 cells with BK increased the synthesis of both IL-6 and PGE(2) and the increase in both was blocked by HOE140 (B2R antagonist), but not by Des-Arg(9)-[Leu(8)]-BK (B1R antagonist). U-73122, a phospholipase C (PLC) inhibitor, suppressed BK-induced IL-6 and PGE(2) synthesis in SaM-1 cells. In addition, BK caused an increase in the intracellular Ca(2+) concentration ([Ca(2+)]i), which was inhibited by pretreatment with HOE140 or 2-aminoethoxydiphenyl borate (2-APB), an inositol 1,4,5-trisphosphate (IP(3)) receptor (IP(3)R) blocker. Furthermore, both SB203580 (an inhibitor of p38 mitogen-activated protein kinase [MAPK]) and PD98059 (an inhibitor of MEK, upstream of ERK) attenuated the BK-induced IL-6 and PGE(2) synthesis. BK treatment resulted in the phosphorylation of p38 MAPK and extracellular signal-regulated kinase (ERK)1/2, and 2-APB could suppress BK-induced phosphorylation of ERK1/2. These findings suggest that BK increased both IL-6 and PGE(2) synthesis in osteoblastic cells via B2R and that PLC, IP(3)-induced [Ca(2+)]i, MEK, and MAPKs were involved in the signal transduction in these cells.
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PMID:Activation of osteoblastic functions by a mediator of pain, bradykinin. 1534 32

Current treatment of osteosarcoma is associated with poor prognosis, especially due to the increased risk of developing other cancers with chemotherapy. Therefore, new, safe and effective treatment strategies are needed. We investigated the effect of a unique mixture of nutrients containing lysine, proline, arginine, ascorbic acid, and epigallocatechin gallate (EGCG) on human osteosarcoma cell lines U-2OS, MNNG-HOS, and Ewing's sarcoma SK-ES-1 by measuring: cell proliferation, expression of matrix metalloproteinase-2 (MMP-2), MMP-9, and invasive and angiogenesis potential. Cell proliferation was evaluated by MTT assay, matrix metalloproteinases (MMP) expression by gelatinase zymography, VEGF expression by ELISA, and invasion through Matrigel. Cells were also treated with phorbol 12-myristate 13-acetate (PMA) to study enhanced MMP and VEGF expression. The invasion of osteosarcoma U-2OS and MNNG-HOS cells through Matrigel was significantly reduced in a dose-dependent fashion, with 100% inhibition of invasion of U-2OS cells at 100 microg/ml, and MNNG cells at 50 microg/ml concentration of the synergistically acting nutrient mixture. Ewing's sarcoma SK-ES-1 cells were not invasive. Nutrient synergy (NS) exhibited a dose response antiproliferative effect on osteosarcoma U-2OS cells, reaching 67% at 1000 microg/ml of NS; no significant suppression of cell proliferation was seen with MNNG or Ewing's sarcoma cells. Zymography showed dose-dependent inhibition of MMP secretion by all three cell lines in the presence of NS. VEGF secretion by U-2OS cells was completely blocked at 500 microg/ml of NS. Our results suggest NS is an excellent candidate for therapeutic use in the treatment of osteosarcoma, by inhibiting cancer cell invasion, and secretion of MMPs and VEGF, all critical parameters for cancer control and prevention.
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PMID:Antitumor effect of nutrient synergy on human osteosarcoma cells U-2OS, MNNG-HOS and Ewing's sarcoma SK-ES.1. 1564 7

Structural changes in the extracellular matrix (ECM) are necessary for cell migration during tissue remodeling. MMPs, VEGF, Ki-67 (proliferative protein), and constituents of ECM play a critical role in angiogenesis and underlie neoplastic invasion and metastasis. This prompted us to investigate the effect of a diet containing lysine, proline, arginine, ascorbic acid, and green tea extract (NM) on the growth of tumors induced by implanting human osteosarcoma MNNG in athymic nude mice and the expression of MMPs, VEGF, Ki-67 and fibronectin in these tumors, as well as the production of mucin (by PAS staining). We also investigated the effect of the supplemented diet on serum ascorbic acid, total protein content, alkaline phosphatase activity, and liver enzymes. Athymic male nude mice (n = 12) were inoculated with 3 x 10(6) osteosarcoma cells MNNG-HOS and randomly divided into group A (fed a regular diet) and group B (fed a regular diet supplemented with 0.5% NM). Four weeks later, the mice were sacrificed. Results showed that NM inhibited the growth and reduced the size of tumors in nude mice. Histological evaluation revealed increased mitotic index, MMP-9, and VEGF secretion in the control group tissues. Results demonstrate that the nutrient mixture of lysine, proline, arginine, ascorbic acid, and green tea extract tested strongly suppressed the growth of tumors without adverse effects in nude mice, suggesting potential as an anticancer agent.
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PMID:Effect of ascorbic acid, lysine, proline, and green tea extract on human osteosarcoma cell line MNNG-HOS xenografts in nude mice: evaluation of tumor growth and immunohistochemistry. 1701 99

The aim of the present study was to test the hypothesis that the proliferation of a human osteoblast cell line (HOS cells) stimulated with hydroxyapatite (HA) may be regulated by nitric oxide (NO). The cells were cultured on the surface of HA. Medium or cells alone were used as controls. L-arginine, D-arginine, 7-NI (an nNOS inhibitor), L-NIL (an iNOS inhibitor), L-NIO (an eNOS inhibitor) or carboxy PTIO, a NO scavenger, was added in the HA-exposed cell cultures. The cells were also precoated with anti-human integrin alphaV antibody. The levels of nitrite were determined spectrophotometrically. Cell proliferation was assessed by colorimetric assay. The results showed increased nitrite production and cell proliferation by HA-stimulated HOS cells up to day 3 of cultures. Anti-integrin alphaV antibody, L-NIO, or carboxy PTIO suppressed, but L-arginine enhanced, nitrite production and cell proliferation of HA-stimulated HOS cells. The results of the present study suggest, therefore, that interaction between HA and HOS cell surface integrin alphaV molecule may activate eNOS to catalyze NO production which, in turn, may regulate the cell proliferation in an autocrine fashion.
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PMID:The role of nitric oxide on the proliferation of a human osteoblast cell line stimulated with hydroxyapatite. 1878 May 64

We report a case of a 31-year-old pregnant woman who was admitted to our perinatology outpatient clinic because of a fetal ventricular septal defect and limb reduction in the upper extremities of fetus revealed by ultrasonographic investigation diagnosed in the 16(th) week of gestation. First child of the family was diagnosed with Holt-Oram syndrome who had atrial septal defect and upper limb anomalies, whereas the father was documented to have arrhythmia and shortening of upper limbs. The pregnancy was terminated in the 16(th) week of gestation with the consent of the family. We performed mutation analysis in T-box transcription factor-5 (TBX5) gene coding exons, including exon/intron boundaries from peripheral blood or skin fibroblasts. The sequence analysis revealed c.241 adenine (A)>thymine (T) [p. arginine (Arg) 81 Tryptophan (Trp)] alteration in exon-3 of the TBX5 gene in affected family members and fetus. This is a novel mutation causing Holt-Oram syndrome.
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PMID:A novel mutated sequence in the T-box transcription factor-5 (TBX-5) gene (c.241A>T) in Holt-Oram syndrome. 2702 70