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

Maximum collagen synthesis and maximum accumulation of insoluble collagen occur at different phenotypic stages in developing osteoblastic cell cultures. Insoluble collagen accumulation depends in part on the activity of extracellular enzymes including procollagen N-proteinases, procollagen C-proteinase (derived from the BMP1 gene), and lysyl oxidase. In addition to its action on procollagen, procollagen C-proteinase processes prolysyl oxidase to mature 32-kDa lysyl oxidase. The regulation of extracellular activities that control insoluble collagen accumulation has not been studied extensively. The present study compares molecular events that control production of a collagenous mineralized extracellular matrix in vitro among five different murine osteosarcoma cell clones derived from the same tumor, but which differ in their ability to produce an insoluble mineralized matrix. Levels of insoluble type I collagen, insoluble calcium, bone morphogenetic protein 1 (BMP-1), and lysyl oxidase expression, lysyl oxidase biosynthesis, lysyl oxidase activity, and prolysyl oxidase processing activity were determined. Results surprisingly indicate that lysyl oxidase activity is not related closely to lysyl oxidase messenger RNA (mRNA) levels among the different cell clones. However, it appears that BMP-1-dependent prolysyl oxidase processing could contribute to the observed lysyl oxidase activity. Highest collagen and BMP-1 mRNA levels, prolysyl oxidase processing activity, and lysyl oxidase activity occurred in a cell clone (K8) that showed the highest levels of insoluble collagen accumulation. Culture media from a cell clone (K37) that accumulates little insoluble collagen or calcium but expresses high levels of lysyl oxidase mRNA contained low molecular weight fragments of lysyl oxidase protein and showed low lysyl oxidase activity. By contrast the K14 cell line exhibits relatively high lysyl oxidase activity and collagen accumulation, but low levels of mature lysyl oxidase protein. Together, these studies indicate that catabolic as well as anabolic activities are important in regulating insoluble collagen accumulation in osteoblastic cells. In addition, results suggest that products of genes homologous to lysyl oxidase may contribute to observed lysyl oxidase activity.
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PMID:Molecular events that contribute to lysyl oxidase enzyme activity and insoluble collagen accumulation in osteosarcoma cell clones. 1084 Nov 88

Connective tissue growth factor/hypertrophic chondrocyte-specific gene product Hcs24 (CTGF/Hcs24) promotes the proliferation and differentiation of chondrocytes and endothelial cells which are involved in endochondral ossification (Shimo et al., 1998, J Biochem 124:130-140; Shimo et al., 1999, J Biochem 126:137-145; Nakanishi et al., 2000, Endocrinology 141:264-273). To further clarify the role of CTGF/Hcs24 in endochondral ossification, here we investigated the effects of CTGF/Hcs24 on the proliferation and differentiation of osteoblastic cell lines in vitro. A binding study using (125)I-labeled recombinant CTGF/Hcs24 (rCTGF/Hcs24) disclosed two classes of specific binding sites on a human osteosarcoma cell line, Saos-2. The apparent dissociation constant (Kd) value of each binding site was 17.2 and 391 nM, respectively. A cross-linking study revealed the formation of (125)I-rCTGF/Hcs24-receptor complex with an apparent molecular weight of 280 kDa. The intensity of (125)I-rCTGF/Hcs24-receptor complex decreased on the addition of increasing concentrations of unlabeled rCTGF/Hcs24, but not platelet-derived growth factor-BB homodimer or basic fibroblast growth factor. These findings suggest that osteoblastic cells have specific receptor molecules for CTGF/Hcs24. rCTGF/Hcs24 promoted the proliferation of Saos-2 cells and a mouse osteoblast cell line MC3T3-E1 in a dose- and time-dependent manner. rCTGF/Hcs24 also increased mRNA expression of type I collagen, alkaline phosphatase, osteopontin, and osteocalcin in both Saos-2 cells and MC3T3-E1 cells. Moreover, rCTGF/Hcs24 increased alkaline phosphatase activity in both cells. It also stimulated collagen synthesis in MC3T3-E1 cells. Furthermore, rCTGF/Hcs24 stimulated the matrix mineralization on MC3T3-E1 cells and its stimulatory effect was comparable to that of bone morphogenetic protein-2. These findings indicate that CTGF/Hcs24 is a novel, potent stimulator for the proliferation and differentiation of osteoblasts in addition to chondrocytes and endothelial cells. Because of these functions, we are re-defining CTGF/Hcs24 as a major factor to promote endochondral ossification to be called "ecogenin: endochondral ossification genetic factor."
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PMID:Effects of CTGF/Hcs24, a hypertrophic chondrocyte-specific gene product, on the proliferation and differentiation of osteoblastic cells in vitro. 1086 44

Metastasis is a major cause of mortality and morbidity in osteosarcoma (OS) patients. To monitor tumor dissemination, we assessed the circulating tumor burden in OS patients by semiquantitative reverse transcription-PCR using osteocalcin, osteonectin, osteopontin, and type I collagen (COLL) mRNAs as molecular markers. We distinguished levels of the mRNAs in peripheral blood between OS patients and healthy subjects using an OS-derived cell line (Saos-2) as a reference standard. We prospectively analyzed 40 peripheral blood samples from 11 OS patients at diagnosis and 29 healthy subjects. In all 29 (100%) healthy subjects, we detected osteocalcin, osteonectin, and osteopontin mRNAs that were most likely attributed to illegitimate transcription in normal hematopoietic cells. In contrast, we found low COLL mRNA levels in only 35% (10 of 29) of healthy subjects, but significantly higher COLL mRNA levels in 91% (10 of 11) of OS patients (P < 0.0001). The reverse transcription-PCR assay for COLL mRNA was sensitive down to the detection of 10 Saos-2 cells among 10(6) normal peripheral blood nucleated cells. The upper limit of COLL mRNA determined among the healthy subjects was found exceeded by six OS patients. The substantially elevated COLL mRNA levels in peripheral blood seemed to originate from circulating malignant cells in these six OS patients, all of whom subsequently developed clinical metastases within 12 months of diagnosis (P = 0.002). Conversely, no metastases were detected in the remaining OS patients with normal COLL mRNA levels. Quantification of COLL mRNA may prove valuable for diagnosing OS micrometastasis and assessing prognosis.
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PMID:Quantitative analysis of circulating tumor cells in peripheral blood of osteosarcoma patients using osteoblast-specific messenger RNA markers: a pilot study. 1087 67

Osteosarcoma cells are useful for investigating bone metabolism as malignant counterpart of osteoblasts. In hematogenous metastases of osteosarcoma cells, the cells need to adjust to various changes in pericellular environment. The changes in pericellular environment may change intracellular environment and consequently the secretion of matrix metalloproteinases (MMPs) which destroy extracellular matrices. In this report, a new cell line, KOS-1, derived from human osteoblastic osteosarcoma was established, and we assumed various culture conditions containing ingredients of the extracellular matrix to make a comparative study on MMPs detected from the culture supernatants. A wide spectrum of MMPs, including MMP-1 and -3 which were increased in the presence of interleukin 1 beta, was detected in this cell line. Production of MMP-1, the enzyme which decomposes types I, II, III and X collagen, by the cells, was increased in the presence of type I collagen. MMP-3 (stromelysin-1) which degrades types III and IV collagen, laminin, fibronectin, proteoglycan, etc. was produced more abundantly in the presence of type IV collagen. MMP-2 (72-kd type IV collagenase/gelatinase A) activity was found to be increased in the presence of gelatin and type IV collagen. The MMPs production in cultured osteosarcoma cells was changed depending on the culture conditions. This indicates that the same osteosarocma cells produce different amounts and kinds of enzymes involved in local infiltration and remote metastases and increase the production of the enzymes most required under a specific environment.
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PMID:Establishment of an osteoblastic osteosarcoma cell line and effects of cell culture conditions on secretion of matrix metalloproteinases from the cultured osteosarcoma cells. 1094 49

Glucocorticoids have an essential role in skeletal development and function but are detrimental in excess. In several tissues, glucocorticoid action is dependent upon the expression of 11beta-hydroxysteroid dehydrogenase (11beta-HSD) isozymes, which interconvert active cortisol (F) and inactive cortisone (E). We previously demonstrated the expression of 11beta-HSD isozymes in human osteosarcoma cell lines, osteoblast cultures, and fetal bone. We now characterize 11beta-HSD expression in adult human bone using specific antihuman 11beta-HSD antibodies, riboprobes, and enzyme activity studies. In addition, the effect of 11beta-HSD on bone metabolism in vivo was assessed using the 11beta-HSD inhibitor carbenoxolone in eight normal male volunteers. In fresh normal human bone tissue, both 11beta-dehydrogenase (cortisol-to-cortisone conversion) and reductase (cortisone-to-cortisol conversion) activities were demonstrated. There was considerable interindividual variation in the dehydrogenase, but not reductase, activity. In bone homogenates, activity was NADP-dependent with a K(m) for F of 4.8 +/- 1.2 micromol/L, suggesting the presence of 11beta-HSD1. This was confirmed by reverse transcription-polymerase chain reaction (RT-PCR) analysis. Immunohistochemistry and in situ hybridization studies demonstrated 11beta-HSD1 isozyme expression in cells of the osteoblast lineage and in osteoclasts. The 11beta-HSD2 isozyme was expressed, but only in osteoblasts and at a low level. Ingestion of 300 mg of carbenoxolone by eight normal volunteers for 7 days resulted in a significant decrease in the bone resorption markers, pyridinoline (Pyr) and deoxypyridinoline (DPyr) (change in urinary Pyr/creatinine -1.55 +/- 0.55 [mean +/- SE], for DPyr/creatinine -0. 4 +/- 0.14 nmol/mmol; p < 0.05 for both), with no overall change in the bone formation markers C- and N-terminal propeptides of type I collagen (PICP and PINP). These data suggest that local tissue metabolism of glucocorticoids is likely to be important in determining the sensitivity of both osteoblasts and osteoclasts to glucocorticoids. In particular, variation in 11beta-HSD isozyme expression and activity may explain individual variation in susceptibility to glucocorticoid-induced osteoporosis.
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PMID:Expression and functional consequences of 11beta-hydroxysteroid dehydrogenase activity in human bone. 1096 48

Particulate wear debris generated mechanically from prosthetic materials is phagocytosed by a variety of cell types within the periprosthetic space including osteoblasts, which cells with an altered function may contribute to periprosthetic osteolysis. Exposure of osteoblast-like osteosarcoma cells or bone marrow-derived primary osteoblasts to either metallic or polymeric particles of phagocytosable sizes resulted in a marked decrease in the steady-state messenger RNA (mRNA) levels of procollagen alpha1[I] and procollagen alpha1[III]. In contrast, no significant effect was observed for the osteoblast-specific genes, such as osteonectin and osteocalcin (OC). In kinetic studies, particles once phagocytosed, maintained a significant suppressive effect on collagen gene expression and type I collagen synthesis for up to five passages. Large particles of a size that cannot be phagocytosed also down-regulated collagen gene expression suggesting that an initial contact between cells and particles can generate gene responsive signals independently of the phagocytosis process. Concerning such signaling, titanium particles rapidly increased protein tyrosine phosphorylation and nuclear transcription factor kappaB (NF-kappaB) binding activity before the phagocytosis of particles. Protein tyrosine kinase (PTK) inhibitors such as genistein and the NF-kappaB inhibitor pyrrolidine dithiocarbamate (PDTC) significantly reduced the suppressive effect of titanium on collagen gene expression suggesting particles suppress collagen gene expression through the NF-kappaB signaling pathway. These results provide a mechanism by which particulate wear debris can antagonize the transcription of the procollagen alpha1[I] gene in osteoblasts, which may contribute to reduced bone formation and progressive periprosthetic osteolysis.
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PMID:Particulate wear debris activates protein tyrosine kinases and nuclear factor kappaB, which down-regulates type I collagen synthesis in human osteoblasts. 1097 95

We have investigated the effect of transforming growth factor-beta1 (TGF-beta1) on the in vitro adhesion activity of the rat osteosarcoma cell lines (ROS 17/2.8) to extracellular matrix substrata, including fibronectin, type I and IV collagen, as well as laminin. The interaction of Arg-Gly-Asp (RGD) and rhodostomin, an RGD containing snake venom, with TGF-beta1 on the cell adhesion was also evaluated. The results showed that incubation with various concentration of TGF-beta1 (1-15 ng/ml) significantly increased the adhesion activity (1.4 to 2.5 folds) of ROS 17/2.8 to fibronectin and type I collagen (p<0.01), whereas the adhesion activity to laminin and type IV collagen was slightly elevated (1.1 to 1.5 folds). The peak effect of TGF-beta1 on the cell adhesion occurred after pretreatment of ROS 17/2.8 with TGF-beta1 for 6 hours. Treatment with Arg-Gly-Asp-Ser (RGDS) and rhodostomin effectively suppressed the TGF-beta1-enhanced adhesion activity to fibronectin and type I collagen. This study demonstrated that the up-regulated cell adhesion activity of ROS 17/2.8 cells by the TGF-beta1 can be inhibited by the rhodostomin.
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PMID:Rhodostomin inhibits the transforming growth factor-beta1-enhanced adhesion activity of ROS 17/2.8 osteosarcoma cells. 1099 55

The effects of recombinant human bone morphogenetic protein-2 (rhBMP-2) on cell growth were studied in three human osteosarcoma cell lines, NOS-1, HuO9, and HuO-3N1; one human prostate cancer cell line, PC-3; and one human breast cancer cell line, OCUB-1M. The growth of these cell lines was not promoted by rhBMP-2 at concentrations of 50, 100, 250, and 500 ng/ml, as evaluated by colorimetric 3 (4,5-dimethyl-thiazol-2-yl)-2,5 diphenyl tetrazolium bromide (MTT) assay. Furthermore, the protein induced osteogenic differentiation, characterized by increased alkaline phosphatase activity, and increased production of type I collagen and gamma-carboxylated osteocalcin in NOS-1 cells. The results of this study may suggest the feasibility of using rhBMP-2 for the reconstruction of bone defects caused by malignant tumors, although the data are still preliminary and require further investigation.
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PMID:Effects of bone morphogenetic protein-2 on human tumor cell growth and differentiation: a preliminary report. 1118 Sep 25

An osteosarcoma cell line has been established from a soft tissue tumor that occurred spontaneously in a BALB / c mouse. This cell line showed ossification when transplanted into syngeneic mice. To examine the mechanism of bone formation, the expression of mRNAs for osteoblastic and chondroblastic markers and factors associated with ossification has been investigated. In culture, the cells exhibited a spindle shape in the growth phase, but had a polygonal shape in the stationary phase. Reverse transcription-polymerase chain reaction analysis showed that the cells expressed mRNAs for pro-alpha1(I) chain of type I collagen, alkaline phosphatase, osteopontin, osteocalcin, and core binding factor alpha1, suggesting differentiation into the stage of osteoblasts during the stationary phase. After transplantation, histological examination revealed small foci of pale blue material and basophilic networks that were scattered in the tumor tissues at one week. The former stained positive with alcian blue, suggesting a chondroid matrix. Pro-alpha1(II) chain of type II collagen mRNA was expressed at one week. A large part of tumors at two and three weeks consisted of basophilic networks, which stained positive via von Kossa's method, indicating a calcified woven bone. In situ hybridization analysis showed strong expression of osteopontin and osteocalcin mRNAs in tumor cells surrounding the bone matrix. Bone morphogenetic protein-6 and -7 mRNAs were detected in transplanted tumors, but not in cultured cells. These results suggest that the cell line has the properties of an osteoblastic lineage when cultured in vitro and has an ossifying ability through endochondral bone formation processes when transplanted in vivo.
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PMID:A murine osteosarcoma cell line with a potential to develop ossification upon transplantation. 1142 54

Parathyroid hormone (PTH)-related peptide (PTHrP) can modulate the proliferation and differentiation of a number of cell types including osteoblasts. PTHrP can activate a G protein-coupled PTH/PTHrP receptor, which can interface with several second-messenger systems. In the current study, we have examined the signaling pathways involved in stimulated type I collagen and alkaline phosphatase expression in the human osteoblast-derived osteosarcoma cells, MG-63. By use of Northern blotting and histochemical analysis, maximum induction of these two markers of osteoblast differentiation occurred after 8 h of treatment with 100 nM PTHrP-(1-34). Chemical inhibitors of adenylate cyclase (H-89) or of protein kinase C (chelerythrine chloride) each diminished PTHrP-mediated type I collagen and alkaline phosphatase stimulation in a dose-dependent manner. These effects of PTHrP could also be blocked by inhibiting the Ras-mitogen-activated protein kinase (MAPK) pathway with a Ras farnesylation inhibitor, B1086, or with a MAPK inhibitor, PD-98059. Transient transfection of MG-63 cells with a mutant form of Galpha, which can sequester betagamma-subunits, showed significant downregulation of PTHrP-stimulated type I collagen expression, as did inhibition of phosphatidylinositol 3-kinase (PI 3-kinase) by wortmannin. Consequently, the betagamma-PI 3-kinase pathway may be involved in PTHrP stimulation of Ras. Collectively, these results demonstrate that, acting via its G protein-coupled receptor, PTHrP can induce indexes of osteoblast differentiation by utilizing multiple, perhaps parallel, signaling pathways.
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PMID:Induction of osteoblast differentiation indexes by PTHrP in MG-63 cells involves multiple signaling pathways. 1150 Mar 4


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