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)

Juxtacortical osteosarcoma occurred on the right tibia and fibula of a 20-22 years old man found in a medieval period cemetery of Budapest. MACROSCOPIC DESCRIPTION: The tumor is located circumferentially on the midshaft of the tibia and fibula and appears cone-shaped. The lesion measured 160 mm in length and 3-5 mm in height. The surface of the tumor is irregular, rough, in some areas shows spicules. These spicules averaged 2-4 mm in length and 1-2 mm in diameter. The anterior and medial surface of the tibia is completely covered by osseous tumor. RADIOGRAPHY: The X-ray study demonstrates the medullary involvement, with mixed osteolytic and osteoblastic areas. Tumor infiltration of the cortex is also apparent as irregular rarefication and lytic lesions. In some areas a "sunburst" picture could be seen. The X-ray picture is characteristic for juxtacortical osteosarcoma. MICROSCOPIC EXAMINATION: stereomicroscopy of specimens shows a sponge-like structure of the surface. The cortical bone is completely destroyed and deep cavities are seen between spiculous and gyrificated neoplastic bone. The spiculae are varied in length and thickness. Irregular bulky bone trabeculae demonstrating uncontrolled neoplastic reaction could be detected. By light microscopic examination severe destruction, osteolytic lesions are seen both in the cortical bone and in the cancellous bone in the peripheral parts of the tumors. Within the neoplastic bone only few remnants of the primary (normal) bone structure could be demonstrated. No reparative reactions were seen next to the osteolysis, the collagen fibers and lamellas are destroyed. Beside the destruction of original bone larger structures composed of irregular newly built nepotistic bone trabeculae can be detected. The newly formed trabeculae (spiculae) contain a tumorous ground substance (probably osteoid tissue) with few collagen fibers, and these areas are covered with a thin bony lamella. In some areas the neoplastic structures are in intimate contact with the original cancellous bone remnants. IMMUNOHISTOCHEMISTRY: Both the osteosarcoma and chondrosarcoma show osteoid and bone neoformation while in the chondrosarcoma type II collagen could also detected. By immunohistochemical reactions no type II and III collagen, only type I collagen reaction was positive. This means that no cartilaginous tissues were present in the tumor. Scanning electron microscopy of these specimens shows sponge-like structures. The tumor reveals irregular trabecular and spicular texture,the spicules are various in diameter and in some spiculae rounded deposits attached to the surface. In our case we found typical radiological and histological picture of the juxtacortical osteosarcoma.
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PMID:[Juxtacortical osteosarcoma of tibia from a medieval cemetery of Budapest]. 1236 24

To observe the differentiation and gene expression of human osteosarcoma cell line MG-63 in culture. Alkaline phosphatase (ALP) activity was determined by p-nitrophenyl phosphate assay; bone Gla protein (BGP) was measured by radioimmunoassay; type I collagen, matrix metalloproteinase (MMP)-1, tissue inhibitor of matrix metalloproteinase (TIMP)-1 mRNA were examined using semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis; MG-63 cells were stained by the Van GieSon method. Type I collagen mRNA expression achieved a maximum level on the 17th day in MG-63 cells; MMP-1 mRNA was not expressed until the 5th day of culture, and gradually increased; TIMP-1 mRNA was nearly constant; ALP activity gradually up-regulated during 0-12 days, and decreased on the 18th day. By Van GieSon staining, MG-63 cells displayed nodule formation at the 12th day, and became more prominent on the 18th day. The results indicate that human osteosarcoma cell line MG-63 has the osteoblast phenotype; during the differentiation of MG-63 cells, there are the following three principle periods: proliferation, extracellular matrix maturation and mineralization.
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PMID:[Differentiation and gene expression of human osteosarcoma cell line MG-63]. 1253 36

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 examined osteo-chondrogenic differentiation of a human chondrocytic cell line (USAC) by rhBMP-2 in vivo and in vitro. USAC was established from a transplanted tumor to athymic mouse derived from an osteogenic sarcoma of the mandible. USAC usually shows chondrocytic phenotypes in vivo and in vitro. rhBMP-2 up-regulated not only the mRNA expression of types II and X collagen, but also the mRNA expression of osteocalcin and Cbfa1 in USAC cells in vitro. In vivo experimental cartilaginous tissue formation was prominent in the chamber with rhBMP-2 when compared with the chamber without rhBMP-2. USAC cells implanted with rhBMP-2 often formed osteoid-like tissues surrounded by osteoblastic cells positive for type I collagen. rhBMP up-regulated Ihh, and the expression of Ihh was well correlated with osteo-chondrogenic cell differentiation. These results suggest that rhBMP-2 promotes chondrogenesis and also induces osteogenic differentiation of USAC cells in vivo and in vitro through up-regulation of Ihh.
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PMID:Recombinant human bone morphogenetic protein-2 promotes Indian hedgehog-mediated osteo-chondrogenic differentiation of a human chondrocytic cell line in vivo and in vitro. 1500 24

We investigated the differentiation potential into various mesenchymal cell lineages of the clonal cell line (USAC) that was isolated from a human chondrogenic osteosarcoma. USAC cells produced types II and X collagens and proteoglycan, indicating chondrocyte differentiation. Production of type I collagen and osteocalcin by USAC cells demonstrated osteoblastic properties. They also differentiated into adipocytes generating numerous lipid droplets in their cytoplasm. Recombinant human bone morphogenetic protein-2 (rhBMP-2) increased production of proteoglycan, types II and X collagens and osteocalcin. This indicates that rhBMP-2 promotes both chondroblastic and osteoblastic differentiation in USAC cells. rhBMP-2 inhibited adipocyte differentiation. USAC cells transplanted with rhBMP-2 into the peritoneal cavities of athymic mice using diffusion chambers generated cartilage and bone more effectively in the diffusion chambers than those produced without rhBMP-2. Although USAC cells also produced adipose tissue in the diffusion chambers following transplantation with or without rhBMP-2, rhBMP-2 treatment reduced the amounts of adipose tissue. These results demonstrate that USAC is a suitable model to explore regulatory mechanisms involved in human mesenchymal cell differentiation.
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PMID:A human chondrogenic cell line retains multi-potency that differentiates into osteoblasts and adipocytes. 1505 Aug 95

The present study was conducted to determine the effect of the inflammatory mediator interleukin 1alpha (IL-1alpha) on osteogenesis using rat osteoblasts. We examined the effect of IL-1alpha on cell proliferation, alkaline phosphatase (ALPase) activity, mineralized nodule formation, and the expression of extracellular matrix proteins in rat osteosarcoma cell lines. The cells were cultured with alpha-minimum essential medium containing 10% fetal bovine serum with and without 0, 1, 10, and 100 units/ml of IL-1alpha for up to 14 days. The mineralized nodule formation was examined by alizarin red staining, and the calcium content in mineralized nodules was determined using a Calcium C-Test kit. The expression of extracellular matrix proteins was estimated by determining levels of mRNAs using the semiquantitative reverse transcription-polymerase chain reaction. The mineralized nodule formation and the calcium content in mineralized nodules were remarkably suppressed by IL-1alpha after 5 days of culture. The ALPase activity decreased in a dose-dependent manner in the presence of IL-1alpha after 7 days of culture. The expression of type I collagen was decreased after 3 days of culture with IL-1alpha. The expression of bone sialoprotein was slightly decreased at days 3 and 5, and the expression of osteopontin was increased at days 3, 5, and 7 of culture with IL-1alpha. These results suggest that IL-1alpha suppresses osteogenesis through a decrease in ALPase and type I collagen production by osteoblasts.
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PMID:IL-1alpha affects mineralized nodule formation by rat osteoblasts. 1535 Aug 29

Estrogens (E) and mechanical strain (MS) exert direct effects on osteoblast activity, with good evidence of interactions between their respective effects. Osteoblasts express both forms of estrogen receptors (ER) ERalpha and ERbeta, and previous studies have suggested a specific role for each receptor. Therefore, our working hypothesis was that the interactions between E and MS on osteoblast activity vary depending on which ER is preferentially activated. Using human osteosarcoma cells U2OS stably transfected either with ERalpha or ERbeta, we evaluated the effects of cyclical cell loading on a F-3000 Flexercell Strain Unit (1.5% elongation, 10 min/day) in presence of estradiol (E2) 10(-8) M or not. The original U2OS cell line, which does not express ER, was characterized by low alkaline phosphatase (AP) activity. In both U2OS-ERalpha and U2OS-ERbeta cell lines, MS induced similar increases in AP activity and gene expression as measured by real-time quantitative RT-PCR, and a decrease in type I collagen gene expression. MS and E2 had a synergistic effect on AP activity as compared to each stimulus alone. No change in proliferation rate was observed. Neither proliferation nor differentiation of the original U2OS cell line was altered by strain or E2. In summary, our data showing differences in response to MS between the U2OS with no ER expression and the U2OS-ERalpha or -ERbeta cell lines provide additional evidence that ER plays a critical role in mechanotransduction. However, we were not able to demonstrate that interactions between E and MS were dependent on ER type in U2OS osteosarcoma cells.
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PMID:Interactions between estrogen and mechanical strain effects on U2OS human osteosarcoma cells are not influenced by estrogen receptor type. 1554 38

This study describes the molecular mechanism by which treatment with 3-AB, a potent inhibitor of PARP, allows human osteosarcoma MG-63 cells to restrict growth and enter differentiation. Our findings show that in MG-63 cells, aberrant gene expression keeps Rb protein constitutively inactivated through hyperphosphorylation and this promotes uncontrolled proliferation of the cells. After 3-AB-treatment, the poly(ADP-ribosyl)ation of nuclear proteins markedly decreases and this results in an increase in both the hypophosphorylated active form of Rb and pRb/E2F complexes. These effects are accompanied by G1 arrest, downregulation of gene products required for proliferation (cyclin D1, beta-catenin, c-Jun, c-Myc and Id2) and upregulation of those implicated in the osteoblastic differentiation (p21/Waf1, osteopontin, osteocalcin, type I collagen, N-cadherins and alkaline phosphatase). Our study suggests that use of PARP inhibitors may induce a remodeling of chromatin with the reprogramming of gene expression and the activation of differentiation.
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PMID:Differentiative pathway activated by 3-aminobenzamide, an inhibitor of PARP, in human osteosarcoma MG-63 cells. 1567 Aug 17

Several in vitro and in vivo studies have indicated that tobacco smoking may be an important risk factor for the development and severity of inflammatory periodontal disease. In the present study, we examined the effect of nicotine on cell proliferation, alkaline phosphatase (ALPase) activity, mineralized nodule formation, and the expression of extracellular matrix proteins in the human osteosarcoma cell line Saos-2. The cells were cultured with Dulbecco's modified Eagle medium containing 10% fetal bovine serum with 0, 10(-4) M, and 10(-3) M nicotine for up to 14 days. Mineralized nodule formation was examined by alizarin red staining, and the calcium content in mineralized nodules was determined using a calcium E-test kit. The expression of extracellular matrix proteins was estimated by determining the levels of their mRNAs using the real-time polymerase chain reaction. Mineralized nodule formation and calcium content in mineralized nodules were remarkably suppressed by nicotine on days 10 and 14 of culture, respectively. ALPase activity as well as type I collagen and osteopontin expression also decreased in the presence of nicotine after 5, 10, and 14 days of culture, respectively. By contrast, the amount of bone sialoprotein increased during 14 days of culture with nicotine. These results suggest that nicotine suppresses osteogenesis through a decrease in ALPase and type I collagen production by osteoblasts.
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PMID:Nicotine affects mineralized nodule formation by the human osteosarcoma cell line Saos-2. 1594 96

In orthopedic surgery, sterilization of bone used for reconstruction of osteoarticular defects caused by malignant tumors is carried out in various ways. At present, to devitalize tumor-bearing osteochondral segments, extracorporal irradiation or autoclaving is mainly used but both methods have substantial disadvantages, for instance, loss of biomechanical and biological integrity of the bone. In particular, after reimplantation, integration of the implant at the autograft-host junction is often impaired due to alteration of osteoinductivity as a result of its irradiation or autoclaving. As an alternative approach, high hydrostatic pressure (HHP) treatment of bone is suggested, a new technology which is in the preclinical testing stage, with the aim to inactivate tumor cells but leaving the biomechanical properties of bone, cartilage, and tendons intact. We investigated the influence of HHP on the major extracellular matrix (ECM) proteins, fibronectin (FN), vitronectin (VN), and type I collagen (Col-I), present in bone tissue, which are accountable for the biological properties within the bone. FN, VN, and Col-I were subjected to HHP < or = 600 MPa prior to coating of cell culture plates with these matrix proteins. Thereafter, the capacity of HHP-pretreated FN, VN, and Col-I to affect cell proliferation, cell adherence, and spreading of human primary osteoblast-like cells and the human osteosarcoma cell line Saos-2, was tested. Interestingly, even at HHP < or = 600 MPa, all three ECM proteins retained their biological properties because no significant changes were observed between HHP-treated and non-treated FN, VN, and Col-I regarding their biological properties to affect cell adherence, spreading, and proliferation. These data encourage further exploration of the potential of HHP to sterilize tumor-affected bone segments prior to reimplantation. While during this treatment eukaryotic cells including tumor cells will be irreversibly impaired, the bone's biomechanical properties and the biological properties of the ECM proteins FN, VN, and Col-I, respectively, are preserved.
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PMID:Effect of high hydrostatic pressure on biological properties of extracellular bone matrix proteins. 1601 63


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