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)

Tumor necrosis factor-alpha (TNF-alpha) stimulates osteoblast production of interleukin-6 (IL-6), an inflammatory cytokine implicated in osteoclastic bone resorption. Therefore, we tested the hypothesis that TNF-alpha-induced IL-6 production in MG-63 osteosarcoma cells occurs via the p38 mitogen-activated protein kinase (MAPK) pathway. TNF-alpha activated p38 MAPK and stimulated IL-6 secretion by MG-63 cells, and pre-incubation of cells with the p38 MAPK inhibitor abrogated TNF-alpha-dependent IL-6 secretion. Transfection of IL-6 full-length and 5-deletion gene promoter reporter constructs indicated that p38 MAPK activation by TNF-alpha enhanced IL-6 gene expression, and that the p38 MAPK-responsive region resided in the proximal 260-bp segment. Transfection of NFkappaB and C/EBPbeta-sensitive reporter promoter constructs demonstrated that NFkappaB activity was enhanced and that constitutive C/EBPbeta was inhibited by TNF-alpha, with both effects being p38 MAPK-dependent. In conclusion, although p38 MAPK activation by TNF-alpha stimulates IL-6 secretion by MG-63 cells, it has opposing effects on c/EBPbeta and NFkappaB activity.
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PMID:Regulation of TNF-alpha-induced IL-6 production in MG-63 human osteoblast-like cells. 1182 Mar 62

Metal debris from implants has been shown to alter the function of osteoblasts in cell cultures. Its remains unclear, however, if specific forms of released ionic metals are involved in the pathogenesis of periprosthetic osteolysis. We evaluated the relative effects of ionic forms of implant metals by treating human osteoblast-like MG-63 osteosarcoma cells with eight concentrations (0.001-10.0 mM) of Cr(+3), Mo(+5), Al(+3), Ta(+5), Co(+2), Ni(+2), Fe(+3), Cu(+2), Mn(+2), Mg(+2), Na(+2), and V(+3) chloride solutions. The results demonstrated that the metal ions differentially affected osteoblast proliferation, viability, type-I collagen gene expression, and cytokine release. The metal ions were ranked in order from least to most toxic (based on a 50% reduction in viability) as follows: Na < Cr < Mg < Mo < Al < Ta < Co < Ni < Fe < Cu < Mn < V. Metal-induced decreases in osteoblast proliferation were similar in ranking. Nontoxic concentrations of metals had no effect on procollagen alpha1[I] gene expression; only at toxic concentrations did metals produce a decrease in gene expression. The most toxic metals (V, Mn, Fe, and Ni) were also the only metals found to induce IL-6 secretion on a per cell basis (of the cytokines tested, interleukin 6 (IL-6), interleukin beta 1 (IL-1beta), transforming growth factor beta 1 (TGF-beta1), and tumor necrosis factor alpha (TNF-alpha), only IL-6 was detectable in the culture medium after 48 h for any metal at any concentration). Less toxic metals (e.g., Co and Cr) had little effect on IL-6 release, even at high concentrations. In general, metal ions reduced osteoblast function (i.e., proliferation and collagen gene expression) in proportion to the degree of toxicity. These results support the hypothesis that adverse local cellular responses (particularly necrotic responses) associated with metal debris from implanted metallic devices may be due in part to metal ions released from implants or from particulate debris.
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PMID:Concentration- and composition-dependent effects of metal ions on human MG-63 osteoblasts. 1192 Jun 66

The biocompatibility of an orthopedic implant depends on the effect of the implant on bone-forming cells, osteoblasts. Changes in osteoblastic proliferation, maturation and differentiation are important events in ossification that enable monitoring the effect of the implant. Transforming growth factor-beta (TGF-beta) is known to suppress osteoblast proliferation and, on the other hand, to induce the maturation and differentiation of osteoblasts. Moreover, osteoblasts produce TGF-beta, which is embedded in the bone matrix and activated by bone-resorbing osteoclasts. TGF-beta inhibits osteoclastic activity. Here, we show for the first time the effect of nickel titanium shape memory metal (NiTi) on osteoblastic cytokine expression. In this study, we measured the levels of TGF-beta with enzyme-linked immunosorbent assay (ELISA) from a ROS-17/2.8 osteosarcoma cell line cultured on different metal alloy discs. ELISA results were proportioned to total DNA content of the samples. We compared NiTi, to stainless steel (Stst), pure titanium (Ti) and pure nickel (Ni). The TGF-beta1/DNA value in the NiTi group (0.0007 +/- 0.0003) was comparable with those seen in the Stst (0.0008 +/- 0.0001) and Ti (0.0007 +/- 0.0001) groups. The concentration in the Ni group was lower (0.0006 +/- 0.0003), though not statistically significantly so. In addition, the effect of surface roughness on TGF-beta1 production was studied. We compared three different grades of roughness in three differently hot-rolled alloys: NiTi. hot-rolled at 950 degrees C. Ti alloy hot-rolled at 850 degrees C (TiI) and the same Ti alloy hot-rolled at 1,050 degrees C (TiII). We found that increasing roughness of the NiTi surface increased the TGF-beta1 concentration. On the other hand, all roughness groups of TiII showed low levels of TGF-beta1. while a rough TiI surface induced similar TGF-beta1, expression as rough NiTi. Further, these same measurements made with interleukine 6 (IL-6) were found to be under the detection limit in these cultures. We conclude that a rough NiTi surface promotes TGF-beta1 expression in ROS-17/2.8 cells.
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PMID:TGF-beta1 secretion of ROS-17/2.8 cultures on NiTi implant material. 1209 76

Biocompatibility of two variants of accelerated Portland cement (APC) were investigated in vitro by observing the cytomorphology of SaOS-2 osteosarcoma cells in the presence of test materials and the effect of these materials on the expression of markers of bone remodelling. Glass ionomer cement (GIC), mineral trioxide aggregate (MTA) and unmodified Portland cement (RC) were used for comparison. A direct contact assay was undertaken in four samples of each test material, collected at 12, 24, 48 and 72 h. Cell morphology was observed using scanning electron microscopy (SEM) and scored. Culture media were collected for cytokine quantification using enzyme-linked immunosorbent assay (ELISA). On SEM evaluation, healthy SaOS-2 cells were found adhering onto the surfaces of APC variant, RC and MTA. In contrast, rounded and dying cells were observed on GIC. Using ELISA, levels of interleukin (IL)-1beta, IL-6, IL-18 and OC were significantly higher in APC variants compared with controls and GIC (p<0.01), but these levels of cytokines were not statistically significant compared with MTA. The results of this study provide evidence that both APC variants are non-toxic and may have potential to promote bone healing. Further development of APC is indicated to produce a viable dental restorative material and possibly a material for orthopaedic
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PMID:An evaluation of accelerated Portland cement as a restorative material. 1216 33

Apo2 ligand (Apo2L/TRAIL) is a member of the tumor necrosis factor (TNF) cytokine family. Apo2L/TRAIL can selectively induce programmed cell death in transformed cells, although its wide tissue distribution suggests potential physiological roles. We have investigated the expression, in human osteoblast-like cells (NHBC), of Apo2L/TRAIL and the known Apo2L/TRAIL death receptors, DR4 and DR5, and the Apo2L/TRAIL decoy receptors, DcR-1, DcR-2, and osteoprotegerin (OPG). NHBC expressed abundant mRNA corresponding to each of these molecular species. Immunofluorescence staining demonstrated that Apo2L/TRAIL protein was abundant within the cytoplasm of NHBC and OPG was strongly expressed at the cell surface. DR5 and DcR-2 were present in the cell membrane and cytoplasm and DcR-1 was confined to the nucleus. DR4 staining was weak. Neither Apo2L/TRAIL alone, nor in combination with chemotherapeutic agents of clinical relevance to treatment of osteogenic sarcoma, induced cell death in NHBC, as assessed morphologically and by activation of caspase-3. In contrast, the human osteogenic sarcoma cell lines, BTK-143 and G-292, were sensitive to exogenous Apo2L/TRAIL alone, and to the combined effect of Apo2L/TRAIL/cisplatin and Apo2L/TRAIL/doxorubicin treatments, respectively. In NHBC, we observed strong associations between the levels of mRNA corresponding to the pro-apoptotic molecules, Apo2L/TRAIL, DR4, and DR5, and those corresponding to pro-survival molecules, DcR-1, DcR-2, OPG, and FLIP, suggesting that the balance between pro-survival and pro-apoptotic molecules is a mechanism by which NHBC can resist Apo2L/TRAIL-mediated apoptosis. In contrast, osteogenic sarcoma cells had low or absent levels of DcR-1 and DcR-2. These results provide a foundation to explore the role of Apo2L/TRAIL in osteoblast physiology. In addition, they predict that therapeutic use of recombinant Apo2L/TRAIL, in combination with chemotherapeutic agents to treat skeletal malignancies, would have limited toxic effects on normal osteoblastic cells.
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PMID:Human osteoblasts are resistant to Apo2L/TRAIL-mediated apoptosis. 1239 39

A certain number of pediatric cancer patients still succumb to relapse following conventional treatment of their malignancies. One of the mechanisms of relapse is escape from immunity. Adoptive cellular immunotherapy with effector cells has the potential to overcome this escape. In adults, the CD3+ CD56+ cell, a cytokine-induced killer (CIK) cell, appears to be a promising effector cell type with the greatest cytotoxicity. This effector cell type may work in children as well. No similar studies with children have been published. We speculated that expanded CD3+ CD56+ cells obtained from pediatric cancer patients during remission would act similarly against various pediatric tumor cell lines; therefore, we undertook the present study to find support for our speculation. This study was undertaken to generate and expand CD3+ CD56+ CIK cells from normal peripheral blood mononuclear cells (PBL) obtained from 6 children with cancer (2 with acute lymphoblastic leukemia, 2 with large cell lymphoma, and 2 with osteosarcoma) in remission after intensive chemotherapy and to study the cytotoxic activities of these cells against chronic myeloid leukemia cell line K562 t(9;22), 4 pediatric tumor cell lines [infant acute lymphoblastic leukemia RS4 t(4;11), TEL/AML acute lymphoblastic leukemia REH t(12;21), alveolar rhabdomyosarcoma Rh-Cr t(2;13), and Ewing sarcoma EW-Le t(11;22)], and 2 pediatric glioblastoma multiforme cultured cell lines (G74 and G77). CIK cells were generated and expanded in culture medium to which interferon gamma, monoclonal antibody against CD3, and interleukin 2 were added at appropriate times. Cells were counted by flow cytometry. Net lactate dehydrogenase release from target cells incubated with CIK cells was used as an index of CIK cell cytotoxicity against various pediatric tumor cell lines. The results show that after 21 days in culture CD3+ CD56+ CIK cells derived from the 6 pediatric patients accounted for a median of 28.3% of the entire culture (range, 10.7%-36.4%). Before expansion no such cells were found in any of the 6 children. Median lytic activity rates of CIK cells were 45.5% to 64.5%, rates that contrasted drastically to the lytic activity rates of PBL, which were only 8% to 12%. The findings of the present study are encouraging. They provide information for developing adoptive immunotherapy for future clinical trials with pediatric cancer patients, particularly those patients with minimal residual disease after intensive chemotherapy or stem cell transplantation (especially nonmyeloablative transplantation procedures).
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PMID:Generation of CD3+ CD56+ cytokine-induced killer cells and their in vitro cytotoxicity against pediatric cancer cells. 1262 54

Permanent osteoblastic cell lines are potential tools to study the interactions between osteoblastic and hematopoietic cells in the bone marrow cavity. In a recent work we have shown that the osteosarcoma cell line CAL72 may be more closely related to normal osteoblasts than the osteosarcoma cells previously described. In the present work we continued the characterisation of the CAL72 cell line with regard to its effects on various hematopoietic cells, in coculture experiments. We show here that CAL72 cells, in contrast to MG-63 or SaOS-2 osteosarcoma cell lines, do not inhibit hematopoietic colony formation and sustain the limited expansion of hematopoietic progenitors in a similar way to that described for normal osteoblasts. We also demonstrate that CAL72 cells induce the monocytic differentiation of the promyelocytic HL-60 cell line like MG-63 and SaOS-2, but support a better maturation and a longer survival of the differentiated cells than the two other osteosarcoma cell lines. In order to better understand the differential effects observed between CAL72 and MG-63 or SaOS-2, we analysed the cytokine and chemokine mRNA expression of these cells using the RNase protection quantitative assay. We show here that the expression profile of CAL72 is clearly different from that of MG-63 or SaOS-2 and may explain, at least in part, its specific effects on hematopoietic cells. Taken together these experiments confirm that CAL72 has particular properties and is an interesting tool to study the role of osteoblastic cells in hematopoietic cell growth and differentiation.
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PMID:CAL72: a human osteosarcoma cell line with unique effects on hematopoietic cells. 1263 Dec 58

Bone hybrids made of bioceramics seeded with mesenchymal or osteoblastic cells are very promising alternatives to autologous bone graft. Along this line, the development of in vitro models, dedicated to analyze the influence of these biomaterials on osteogenic cells, will help to improve the performance of these bone substitutes. In the present work we analyzed the effects of a macroporous biphasic calcium phosphate ceramic (BCP, Triosite) on three different human osteosarcoma cell lines and on human primary osteogenic cells and compared this culture substratum to traditional culture on plastic. We showed that all these osteoblastic cells adhere and proliferate on the trabecular BCP blocks, with a different spatial organization for osteosarcoma cells compared to normal osteogenic cells. We also demonstrated that osteoblastic marker genes such as Cbfa1, type I collagen, osteonectin, osteopontin, and osteocalcin were expressed at similar levels by these cells cultured on either substratum, suggesting that adhesion to BCP does maintain the osteoblastic phenotype of these cells. Next, we provided the first evidence of differences of cytokine expression profiles revealed on this Ca-P ceramic as compared to expression in classical culture. These modifications affected the expression of cytokines such as TGF-beta1, G-CSF, and IL-3 and were quantitatively different between osteosarcoma cells and normal osteogenic cells. Given the role of these cytokines in bone biology and in hematopoiesis, these results obtained in vitro suggest that the BCP ceramic studied here could stimulate osteogenesis in vivo by activating cellular processes during bone formation and healing. This study highlights the notion that the nature of the culture substratum must be taken into account when studying bone cell biology in vitro. Owing to the nature and spatial organization of the BCP, our hypothesis is that culture on BCP is closer to the physiological situation than culture on plastic.
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PMID:Modification of gene expression induced in human osteogenic and osteosarcoma cells by culture on a biphasic calcium phosphate bone substitute. 1281 Jan 67

We investigated the effect of the proinflammatory cytokine interleukin 17 (IL-17) on the lysis of osteosarcoma cells by human NK cells. NK cells and U-2 OS, MG-63, HOS osteosarcoma cell lines express the IL-17 receptor, the highest amount being found on U-2 OS. Pre-incubation of NK cells with IL-17 did not affect the cytotoxicity against osteosarcomas, that was increased when U-2 OS were pre-incubated with IL-17. In IL-17 treated U-2 OS osteosarcoma cells FACS analysis demonstrated an increased expression of fibronectin among the panel of adhesion molecules assayed, and the treatment with anti-fibronectin antibodies decreased the NK cytotoxicity. The comparison between interferon gamma (IFN-gamma) treated and IFN-gamma/IL-17-treated U-2 OS showed a decreased susceptibility to NK lysis associated with a reduced expression of CD49f on U-2 OS treated with IFN-gamma/IL-17. IL-17 appears to be a modulator of NK adhesion molecules on U-2 OS cells but antagonizes with IFN-gamma on NK lysis.
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PMID:IL-17 enhances the susceptibility of U-2 OS osteosarcoma cells to NK cell lysis. 1293 Mar 59

Cytokines play important roles in the expression of adhesion molecules and the function of anti-tumor effector cells in the immune system. In this study, the influence of interleukin-12 (IL-12) and IL-18 on the expression of ICAM-1 and natural killer (NK)-cell mediated lysis in a human osteosarcoma cell line (HOS) was evaluated. ICAM-I expression of HOS cells were analyzed by flow cytometry following treatment with IL-12, IL-18 or both, and in co-cultures with peripheral lymphocytes. NK-cell activation in response to IL-12 and IL-18 was investigated by selective flow cytometry using propidium iodide. ICAM-1 expression on HOS cells was significantly enhanced by IL-12, but only when co-cultured in cell-to-cell contact with peripheral lymphocytes. Antibodies to interferon-gamma abrogated this effect. If HOS cells and peripheral lymphocytes were separated in co-cultures, IL-18 could substitute for cell-to-cell contact, facilitating IL-12-mediated enhancement of ICAM-1. Addition of IL-18 also enhanced NK-mediated cytolysis of HOS cells. These findings demonstrate that IL-12 can enhance the expression of ICAM-1 in the presence of IFN-gamma and, with IL-18, enhances NK anti-tumor activity. Immunomodulation via cytokine therapy may lead to improved eradication of chemotherapy-resistant osteosarcomas.
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PMID:Interleukin-12 and interleukin-18 change ICAM-I expression, and enhance natural killer cell mediated cytolysis of human osteosarcoma cells. 1466 53


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