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

Saos-2 cultured human osteosarcoma cells contain an extractable bone inducing agent that can induce heterotopic bone in the muscle of Nu/Nu mice. A semipurified GuHCl extract of Saos-2 cells also can promote healing and complete bony union in otherwise non-healing surgically induced defects of rat femur. Northern blot analyses indicate expression of mRNAs for bone morphogenetic proteins (BMP)-1, 2, 3, 4, 6 and transforming growth factor beta (TGF beta) in Saos-2 cells, and BMP-2, 3, 4, 5, 7 and TGF beta in nonosteoinductive U20S human osteosarcoma cells. Saos-2 cells exceeded U20S cells in expression levels of BMP-1, 3, 4 and TGF beta, whereas U20S cells expressed higher levels of BMP-2, 6 and also expressed trace amounts of BMP-5 and 7 not seen in Saos-2 cells. The authors hypothesize that Saos-2 cells contain an optimal admixture of known bone growth factors plus possible other unknown components that, acting alone or in combination with bone morphogenetic protein and/or TGF beta, can induce bone. Although bone inducing agent-induced heterotopic bones have half lives of only a few weeks, the reparative bone induced by bone inducing agent in femoral defects gives every indication of being permanent and self-sustaining. This suggests a fundamental difference between heterotopic and orthotopic osteoprogenitor cells with those involved in orthotopic bone repair more closely resembling the committed or determined osteoprogenitor cells of marrow as described by Friedenstein.
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PMID:The mechanism of bone induction and bone healing by human osteosarcoma cell extracts. 764 70

We recently showed that osteogenic protein-1(OP-1), a bone morphogenetic protein member of TGF-beta superfamily, induces endochondral bone formation in vivo, and stimulates growth and differentiation of osteoblasts in rat calvarial-derived cell cultures. In the present study, we examined the effect of OP-1 on cell growth and expression of markers that are characteristic of osteoblast phenotype using the clonal rat osteosarcoma cells (ROS 17/2.8). A comparison of OP-1 and TGF-beta 1 effects on cell growth showed that, both OP-1 and TGF-beta 1 inhibited DNA synthesis up to 90 percent and 60 percent of the controls at concentrations of 10 ng/ml and 1 ng/ml, respectively, in serum-free medium. In the presence of 5% serum, TGF-beta 1 did not have any significant inhibitory effects while 40 ng OP-1/ml inhibited the DNA synthesis up to 80% of the controls. Examination of collagen synthesis showed that 40 ng OP-1/ml increased the expression of type I collagen mRNA, and thus increased collagen synthesis (4-fold), as examined by collagenase-digestible protein. Evaluation of markers that are characteristic of the osteoblast phenotype demonstrated that OP-1 stimulated cAMP production in response to PTH (10-fold at 200 ng/ml), alkaline phosphatase specific activity (ALPase) (4-fold at 80 ng/ml), and osteocalcin (OC) synthesis (4.5-fold at 40 ng/ml). Northern blot analysis revealed that OP-1 increased mRNA expression for both ALPase and OC in a dose-dependent manner. These data collectively demonstrate that OP-1 suppresses cell proliferation and stimulates the expression of markers characteristic of osteoblast phenotype in rat clonal osteoblastic osteosarcoma cells (ROS 17/2.8).
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PMID:Osteogenic protein-1 (BMP-7) inhibits cell proliferation and stimulates the expression of markers characteristic of osteoblast phenotype in rat osteosarcoma (17/2.8) cells. 773 48

Osteosarcomas contain variable amounts of bony tissue, but the mechanism of bone formation by osteosarcoma is not well understood. While a number of cultured human osteosarcoma cell lines have been established, they are maintained by different media and differ qualitatively with regard to bone formation. We examined different media for their ability to support bone formation in vitro and found the alpha-modification of Eagle's minimal essential medium supplemented with beta glycerophosphate was best for this purpose, because it contained the proper calcium and phosphate concentrations. Subsequently, we compared seven human osteosarcoma cell lines under the same experimental conditions to clarify their ability to induce bone formation. NOS-1 cells most frequently exhibited features of bone formation in vitro and in nude mice. Collagen synthesis by tumour cells themselves seemed to be the most important factor for bone volume. However, even HuO9 cells, which lacked collagen synthesis and failed to form bone in vitro, successfully formed tumours containing bone in nude mice. Histological analysis of HuO9 cells in diffusion chambers implanted in nude mice and the findings of polymerase chain reaction indicated that the phenomenon was probably due to bone morphogenetic protein.
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PMID:Bone formation in vitro and in nude mice by human osteosarcoma cells. 775 79

The effects of porcine bone morphogenetic protein (BMP) on DNA and collagen synthesis in cultured rat osteogenic sarcoma cells and mink lung epithelial cells were studied and compared with the effects induced by transforming growth factor-beta 1 (TGF-beta 1). In both cells, DNA synthesis was slightly but significantly increased by BMP whereas it was notably decreased by TGF-beta 1. The inhibitory action of TGF-beta 1 overrode the activation of DNA synthesis by BMP when the cells were incubated together with TGF-beta 1 and BMP. In osteogenic sarcoma cells, collagen synthesis was enhanced by both BMP and TGF-beta 1, but the stimulatory action of BMP was weaker than that of TGF-beta 1. In epithelial cells, TGF-beta 1 increased collagen synthesis but BMP induced no significant changes. No synergistic effects of TGF-beta 1 and BMP on collagen synthesis were observed in both cells. The present study demonstrates the possibility of direct actions of BMP and TGF-beta 1 on cultured rat osteogenic sarcoma cells and mink lung epithelial cells in vitro.
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PMID:Differential effects of transforming growth factor-beta 1 and bone morphogenetic proteins in cultured rat osteogenic sarcoma and mink lung epithelial cells. 795 Oct 46

Periosteal sunburst spiculation is a peculiar radiographic feature of osteosarcoma, and it represents a reactive ossification resulting from the action of normal osteoblasts rather than tumor cells. Because bone morphogenetic protein is known to be a potent inducer of ectopic bone formation, the authors hypothesized that bone morphogenetic protein may be involved in the pathogenesis of such reactive bone formation in osteosarcoma. Chinese hamster ovary cells transfected with the bone morphogenetic protein-4 gene were injected into the femurs of athymic nude mice to form experimental bone tumors producing bone morphogenetic protein. Two weeks after intramedullary injection, new bone formation was observed radiographically and histologically within the extraosseous portions of the tumors. This showed a close resemblance to sunburst spiculation in human osteosarcomas. In contrast, the control nontransformed Chinese hamster ovary tumors showed no extraosseous bone formation. Because the induced bone was composed of multiple parallel spicules similar to those found in human bone morphogenetic protein-producing osteosarcomas, these findings suggest that periosteal sunburst spiculation may be the result of bone morphogenetic protein production by osteosarcoma cells.
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PMID:Periosteal sunburst spiculation in osteosarcoma. A possible role for bone morphogenetic protein. 795 86

Recent studies have shown that osteogenic protein (OP)-1 or bone morphogenetic protein (BMP)-7 increases proliferation and differentiation of human bone cells (HBCs) in culture and modulates production of IGF system components. In order to study the mechanism by which OP-1 causes these effects, we sought to test the hypothesis that the effects of OP-1 are mediated at least in part by specific receptors (for OP-1) in HBCs. Binding studies with serum-free cultures of normal HBCs and human osteosarcoma cells showed a maximum binding of 15-25% for [125I]OP-1; the binding was time- and temperature-dependent in different experiments. Scatchard analysis of [125]OP-1 binding to TE85 human osteosarcoma cells showed at least two binding sites, about 30,000 and 60,000 per cell with apparent Kd of 2.5 x 10(-10)M and 1 x 10(-9)M, respectively. [125]OP-1 binding to TE85 cells was displaced by unlabeled OP-1 (16-1000 ng/ml), with a 50% displacement at 250 ng/ml. BMP-2 effectively displaced [125]OP-1 binding to HBCs while TGF-beta 1 did not. Affinity cross-linking studies showed that [125]OP-1 interacted specifically with three binding sites with apparent M(r) of 34, 65 and > 205kDa. The findings of this study demonstrate that the effects of OP-1 on HBCs may be mediated in part via BMP-specific receptors.
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PMID:Evidence that human bone cells in culture contain binding sites for osteogenic protein-1. 802 55

It is well known that the bone matrix contains proteins which can induce ectopic endochondral bone formation in vivo. One class of these proteins is the bone morphogenetic protein (BMP). In order to investigate the physiological function of the BMP, its purification was attempted from an extract of demineralized bone matrix and its actions on the osteoblastic cell line were investigated. To isolate the BMP, a demineralized bone matrix was extracted with 4M guanidine-HCl. A water-insoluble fraction (G-WI) was separated from the demineralized bone extract by dialysis against distilled water and centrifugation. The BMP was purified from G-WI by gel filtration on Sephacryl S-200 HR, cation exchange with Mono-S, heparin affinity column and finally by C1/8 reverse phase chromatography. Peptide sequence analysis revealed that the purified BMP fraction contained "BMP-3" reported by Wozney et al. (1988). In order to investigate its function, the BMP was applied to the rat osteogenic sarcoma cell line UMR108. The BMP inhibited the growth of the UMR108 cells and enhanced the alkaline phosphatase activity in a dose-responsive manner.
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PMID:[Purification of bone morphogenetic protein and investigation of its effects on osteoblastic cell line UMR108]. 848 1

A protein fraction capable of eliciting cartilage or bone formation in vivo was purified more than 100,000-fold from a murine osteosarcoma (Dunn type). Intramuscular implantation of as little as 20 ng of the purified protein with 2 mg of pure skin collagen consistently induced ectopic new bone formation. The apparent molecular size of the purified protein was 32 kd on sodium dodecylsulfate-polyacrylamide gel electrophoresis. On reduction, the 32-kd protein split into subunits with the same partial amino acid sequences, and these partial sequences were identical to those of human bone morphogenetic protein-2B (BMP-4) which is assumed to be a member of the transforming growth factor-beta superfamily.
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PMID:Purification and characterization of a bone-inducing protein from a murine osteosarcoma (Dunn type). 851 28

Bone morphogenetic proteins (BMPs) have important functions for the differentiation of bone cells, but the exact role for bone remodeling and bone healing still needs to be defined. Migration of bone forming cells is an important physiological event both during bone healing and bone remodeling. The chemotatic properties of the bone morphogenetic protein family of growth factors have not been investigated. In this study the chemotactic effects of the bone morphogenetic proteins BMP-2, -4, and -6 have been quantitated toward human osteoblasts, human marrow stromal osteoblasts, and U2-OS human osteosarcoma cells. BMP-2 stimulated the migration of human stromal osteoblasts, human osteoblasts, and U2-OS cells with bell-shaped response curves in a dose-dependent manner with a 300% increase in cell migration at 1.0 ng/mL for human stromal osteoblasts and a 170-180% increase for human osteoblasts and U2-OS cells. At higher concentrations, migration decreased to background levels. BMP-4 and -6 did not show any effect on cellular migration. This study shows that BMP-2 can stimulate in vitro migration of human osteoblasts and human osteosarcoma cells. BMP-2 might play a role in the chemotactic recruitment of especially undifferentiated osteoblasts during bone remodeling and bone healing.
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PMID:Bone morphogenetic protein-2 but not bone morphogenetic protein-4 and -6 stimulates chemotactic migration of human osteoblasts, human marrow osteoblasts, and U2-OS cells. 871 37

Implants of defatted, freeze-dried Saos-2 human osteosarcoma cells grown to confluency induce de novo bone formation in athymic mice. These cells are also richly endowed with bone morphogenetic proteins and express mRNA for bone morphogenetic proteins 1, 2, 3, 4 and 6, as well as for transforming growth factor-beta 1. Our aim was to study whether the ability to induce bone formation is related to the level of expression of bone morphogenetic protein. We studied the osteoinductive abilities and levels of expression of bone morphogenetic protein of Saos-2 cells both during the growth phase and after confluency was reached. Subconfluent cells were at least 70% less effective in their osteoinductive ability than confluent cells. Comparison of bone morphogenetic protein mRNA expression in confluent and subconfluent cells revealed that the latter had lower expression of all the mRNAs studied. The expression of bone morphogenetic protein-1, bone morphogenetic protein-2, and bone morphogenetic protein-6 mRNAs was 2, 3, and 6 to 10-fold lower, respectively, in subconfluent cells. These results suggest that the ability of Saos-2 cells to induce de novo bone formation may be correlated with the relative expression of these proteins; the expression of bone morphogenetic proteins in Saos-2 cells also may be dependent on the cell cycle.
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PMID:Osteoinductive ability of confluent Saos-2 cell correlates with enhanced expression of bone morphogenetic proteins. 876 70


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