Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Demineralized bone powder (DBP) has been shown to induce osteogenesis in a variety of bone defects and extra-osseous sites. Previous investigations have been carried out in animal models which are time-consuming and expensive. We studied the effect of DBP on well-established populations of osteoblast and non-osteoblast-like cells in culture to establish an inexpensive, efficient and reliable assay for bone induction. DBP and BP (non-demineralized powder), of particle size 38-53 microns, were prepared from rat long bones. ROS (rat osteosarcoma) 17/2.8 and ROS 24/1 cell lines were subcultured weekly. For both 17/2.8 (well differentiated) and 24/1 (poorly differentiated) cells, proliferation, i.e. cell count, was significantly greater in DBP enriched medium when compared with control or medium with BP. Cell counts for wells with BP were no different from controls. The increased cell count in DBP-enriched medium was significant on days 2-5 (peak effect 2-3 days). Alkaline phosphatase production reached peak levels after day 3 when proliferation was beginning to taper off. In this study a consistent increase in osteoblast proliferation and alkaline phosphatase production under the influence of DBP was demonstrated. The tissue culture assay for proliferation must now be correlated with bone induction in vivo. In future, the method may be useful for investigating the mechanism of bone induction.
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PMID:Effect of demineralized bone powder on osteoblast-like cells in culture. A potential rapid quality control assay. 170 40

The antigen detected by monoclonal antibodies reacting with human osteosarcoma-associated antigen was shown to be a phosphatidyl-inositol (PI)-glycan-anchored protein, which can be released from the cell surface by PI-specific phospholipase C-treatment. The antigen detected by 2D3 and 2H10 antibodies exhibited alkaline phosphatase activity. Both antibodies strongly reacted with bone-type alkaline phosphatase. However, importantly, immunohistochemical analysis demonstrated that 2D3 and 2H10 did not react with alkaline phosphatase present in kidney or liver. In addition, neither placental nor intestinal alkaline phosphatase was recognized by 2D3 and 2H10 antibodies. These results indicated that two monoclonal antibodies, 2D3 and 2H10, are highly specific for bone-type alkaline phosphatase and can distinguish bone alkaline phosphatase from liver alkaline phosphatase in spite of the fact that liver and bone alkaline phosphatase are encoded by the same gene.
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PMID:Detection of bone-type alkaline phosphatase by monoclonal antibodies reacting with human osteosarcoma-associated antigen. 171 40

Osteoblasts, the bone-forming cells, synthesize the macromolecules of the bone matrix including: type I collagen; osteocalcin; osteonectin; osteopontin; proteoglycan I and II; bone sialoprotein; matrix gla-protein; bone glycoprotein 75; several other proteins, which have not been extensively characterized; growth factors, including transforming growth factor beta and fibroblast growth factor. Osteoblasts also have high levels of the membrane-bound enzyme, alkaline phosphatase, which plays a role in matrix mineralization, and receptors for tissue-specific hormones, such as parathyroid hormone, as well as many other hormones, cytokines and growth factors, which regulate bone growth, differentiation and metabolism. The expression of these various proteins, most of which are not unique to bone but which together characterize the bone phenotype, is induced during osteoblastic differentiation in a stepwise fashion, suggestive of multiple regulatory factors. The detailed sequence of the expression of osteoblastic genes in situ has not been fully characterized. It appears that type I collagen and alkaline phosphatase are expressed early during the commitment to the osteoblastic phenotype, whereas osteopontin and osteocalcin appear late during osteoblastic differentiation. Diversity among "osteoblastic" cells is also apparent, probably not all osteoblastic cells express all the features. A large number of osteoblastic models are currently available to study the expression of osteoblast-related genes in vitro. These include primary cultures from calvaria or trabecular bone from several species, including humans, osteosarcoma-derived cell lines, and experimentally immortalized cells. Some of these in vitro models, especially the calvaria-derived cultures, undergo changes which mimic osteoblastic differentiation in vivo. The study of these and other cell models started providing insights into the regulation of gene expression in osteoblastic cells. In addition to a vast body of information on the conditions required for the expression of various proteins in culture and their regulation by hormones and growth factors, more detailed information on specific genes has recently been obtained. For example, regulation of type I collagen gene expression has been studied in osteosarcoma cell lines where 1,25(OH)2 vitamin D3 was shown to act via specific DNA segment(s) in the 5' flanking region of the gene, while parathyroid hormone affected gene expression by altering the stability of the transcripts. TGF beta 1, which stimulates osteogenesis, was shown to promote the transcription of osteopontin and type I collagen, the latter effect requiring the binding site for the transactivating protein, nuclear factor I.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Gene expression in osteoblastic cells. 180 5

We have previously shown that osteocalcin synthesis is readily induced by 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in MG-63 human osteosarcoma cells (Mahonen et al. (1990) Biochim. Biophys. Acta 1048, 30-37). In the present study, the regulation of osteocalcin synthesis by other hormones of the steroid-thyroid hormone family (retinoic acid, 17 beta-estradiol, triiodothyronine, and dexamethasone) was examined. We found that the other hormones alone had no effects on medium osteocalcin and osteocalcin mRNA concentrations by 96 h of treatment. Compared with 1,25(OH)2D3, however, the combination of 1,25(OH)2D3 with dexamethasone resulted in a greatly reduced medium osteocalcin concentration. Also estradiol and triiodothyronine diminished the stimulatory effect of 1,25(OH)2D3. In contrast, the combination of 1,25(OH)2D3 with retinoic acid resulted in an increased medium osteocalcin concentration. The inhibition of osteocalcin synthesis by dexamethasone and triiodothyronine was accompanied by decreased osteocalcin mRNA levels. Retinoic acid and estradiol, however, did not influence the 1,25(OH)2D3-induced osteocalcin mRNA levels. To examine the specificity of the hormonal effects, the activity of alkaline phosphatase was determined. Both baseline and 1,25(OH)2D3-stimulated alkaline phosphatase activity was found to be inhibited by all other hormones. These results suggest that the steroidal hormones specifically affect osteocalcin synthesis in osteoblastic bone cells, and that complex interactions occur at the level of transcription and/or translation resulting in each case in a finely adjusted rate of osteocalcin synthesis.
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PMID:Modulation of 1,25(OH)2D3-induced osteocalcin synthesis in human osteosarcoma cells by other steroidal hormones. 182 Sep 70

Serum osteocalcin did not show any response to the onset of osteosarcoma in Paget's disease of bone whereas serum alkaline phosphatase increased rapidly. This suggests that osteocalcin is not useful in the diagnosis and management of Paget's osteosarcoma and does not reflect the same osteoblastic processes in bone as serum alkaline phosphatase.
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PMID:Differential response of serum alkaline phosphatase and serum osteocalcin in Paget's osteosarcoma. 185 60

We present a new human osteosarcoma cell line designated OHS-4. These cells showed a high alkaline phosphatase activity that is not regulated by 1,25 dihydroxyvitamin D3. They exhibited a sensitive adenylate cyclase response to parathyroid hormone but not to prostaglandin E2 or human calcitonin. By Northern blot analysis we could detect type I collagen mRNA but none for type III collagen. The cells were able to produce human osteocalcin at a maximum level of 35 ng per million cells when exposed to 2.4 nM 1,25-dihydroxyvitamin D3 for 96 h. We purified this protein from conditioned media using successive chromatography and assessed its identity by partial amino acid sequencing. When injected into nude mice, the cells retained their osteogenic activity and developed calcified tumors. After Von Kossa staining, we observed nonmineralized osteoid deposits and mineralized deposits with a structure similar to that of trabecular bone by light microscopy. On the basis of its osteoblastic characteristics, this new osteosarcoma cell line may represent the human counterpart of the ROS 17/2 cell line. This cell line represents a valuable model for the isolation and characterization of human bone specific proteins.
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PMID:Characterization of a new human osteosarcoma cell line OHS-4. 186 Aug 86

A finite human cell line was established from trabecular bone explants obtained from a 48-year-old woman. These cells, designated BG688, were characterized as osteoblast-like in phenotype using the following independent criteria: (1) the presence of histochemically detectable alkaline phosphatase (AP) activity; (2) response to the calciotropic hormone 1,25-(OH)2D3 as assessed by increased AP activity; (3) synthesis and secretion of the osteoblast-specific marker bone gla protein; and (4) expression of alpha 1(I)-procollagen and alpha 1(III)-procollagen mRNAs in a pattern similar to that of other osteoblast-like cell lines. In addition to these classic osteoblast markers, BG688 cells also possess approximately 2400 high-affinity (Kd = 0.45 nM) 17 beta-estradiol (E2) binding sites per cell. The binding of E2 to these sites is specific, and of the steroid hormone agonists tested, E2 and diethylstilbestrol elicited the greatest amount of competition with radiolabeled E2. BG688 cells were also shown to respond to a physiologic concentration (10 nM) of E2. In vitro translation products of poly(A)+ RNA obtained from control and hormone-treated cells revealed a pleiotropic influence of E2 on the relative abundance of several mRNAs as assessed by two-dimensional gel electrophoretic analysis of their corresponding peptides. E2 also elicits a twofold increase in the steady-state concentration of alpha 1(I)-procollagen mRNA as demonstrated by northern blot hybridization. Thus, we here extend our previous data obtained in osteoblast-like osteosarcoma cells to indicate that a normal osteoblastic cell line is a target for the action of estrogen.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Estrogen binding and estrogenic responses in normal human osteoblast-like cells. 188 16

Micromolar concentrations of aluminum sulfate consistently stimulated [3H]thymidine incorporation into DNA and increased cellular alkaline phosphatase activity (an osteoblastic differentiation marker) in osteoblast-line cells of chicken and human. The stimulations were highly reproducible, and were biphasic and dose-dependent with the maximal stimulatory dose varied from experiment to experiment. The mitogenic doses of aluminum ion also stimulated collagen synthesis in cultured human osteosarcoma TE-85 cells, suggesting that aluminum ion might stimulate bone formation in vitro. The effects of mitogenic doses of aluminum ion on basal osteocalcin secretion by normal human osteoblasts could not be determined since there was little, if any, basal secretion of osteocalcin by these cells. 1,25 Dihydroxyvitamin D3 significantly stimulated the secretion of osteocalcin and the specific activity of cellular alkaline phosphatase in the human osteoblasts. Although mitogenic concentrations of aluminum ion potentiated the 1,25 dihydroxyvitamin D3-dependent stimulation of osteocalcin secretion, they significantly inhibited the hormone-mediated activation of cellular alkaline phosphatase activity. Mitogenic concentrations of aluminum ion did not stimulate cAMP production in human osteosarcoma TE 85 cells, indicating that the mechanism of aluminum ion does not involve cAMP. The mitogenic activity of aluminum ion is different from that of fluoride because (a) unlike fluoride, its mitogenic activity was unaffected by culture medium changes; (b) unlike fluoride, its mitogenic activity was nonspecific for bone cells; and (c) aluminum ion interacted with fluoride on the stimulation of the proliferation of osteoblastic-line cells, and did not share the same rate-limiting step(s) as that of fluoride. PTH interacted with and potentiated the bone cell mitogenic activity of aluminum ion, and thereby is consistent with the possibility that the in vivo osteogenic actions of aluminum ion might depend on PTH. In summary, low concentrations of aluminum ion could act directly on osteoblasts to stimulate their proliferation and differentiation by a mechanism that is different from fluoride.
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PMID:Aluminum stimulates the proliferation and differentiation of osteoblasts in vitro by a mechanism that is different from fluoride. 192 12

We have previously reported that 1,25(OH)2D3 stimulated the cellular alkaline phosphatase (ALP) activity and increased the steady-state level of ALP mRNA in a human osteosarcoma cell line (TE-85), under serum-free conditions. To define the molecular mechanism by which 1,25(OH)2D3 acts to stimulate ALP activity, the time courses of the increases in ALP activity and in the steady-state ALP mRNA level in response to 1,25(OH)2D3 were evaluated. 1,25(OH)2D3 progressively increased the steady-state level of ALP mRNA from 5 to 24 h of treatment, at which time a plateau was observed. In contrast, no significant increase in ALP-specific activity was detected until after 10 h of treatment, at which time the activity increased linearly with time up to 72 h. These time courses are consistent with the premise that the increased ALP activity was the result of increased gene expression. Nuclear runoff analysis indicated that the transcription rate of the ALP gene was more than five-fold higher in the 1,25(OH)2D3-treated cells than in the control cells. In addition, it was found that 1,25(OH)2D3 treatment increased ALP mRNA stability. The 1,25(OH)2D3-induced increase in ALP mRNA stability was not due to an interaction of the 1,25(OH)2D3-receptor complex with the ALP mRNA, since the removal of 1,25(OH)2D3 did not abolish its stabilizing effect. In the presence of cycloheximide, the stabilizing effect of 1,25(OH)2D3 was abolished, suggesting that a 1,25(OH)2D3-inducible protein factor was involved. Based on these findings, we have proposed a model in which 1,25(OH)2D3 stimulated ALP activity in human bone cells through mechanisms involving both (1) increased transcription of the ALP gene and (2) increased stability of ALP mRNA, an effect which requires the de novo synthesis of a protein, a putative ALP mRNA "stabilizing factor."
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PMID:1,25-Dihydroxyvitamin D3 stimulates both alkaline phosphatase gene transcription and mRNA stability in human bone cells. 195 46

Hydroxypropylcellulose mixed beryllium oxide pellets were implanted into the distal metaphysis in the right femurs of 30 rabbits (3 groups, 10 rabbits each): in Group 1 into the internal callus 1 week after production of artificial fracture at a dose of 300 mg, in Group 2 into the bone marrow cavity at a dose of 300 mg, and in Group 3 into the bone marrow cavity at a dose of 50 mg. Osteosarcoma was induced in all of 10 rabbits in Group 1, 7 out of 10 in Group 2, 1 out of 10 in Group 3 at 56 weeks after implantation of BeO. In Group 1, the emergence of tumor and the increase of serum alkaline phosphatase appeared significantly earlier and 80% of the animals with osteosarcoma showed lung metastasis. This experimental method, especially that used in group 1, appears to be useful for the study of human osteosarcoma.
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PMID:[Rabbit osteosarcoma induced by hydroxypropylcellulose mixed beryllium oxide pellet--comparison between implantations into bone marrow cavity and into fracture callus of the femur]. 196 Apr 78


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