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)

The beta-adrenergic blocking agent propranolol was shown in previous studies to increase orthotopic bone formation in rats. To understand the cellular mechanisms underlying this observation, propranolol was tested for its effects on osteoblastic cells, which possess adenylate cyclase-coupled beta-adrenergic receptors. The ability of propranolol to modulate parathyroid hormone (PTH) and isoproterenol effects on adenylate cyclase activity and on alkaline phosphatase expression was studied in the osteoblast-like rat osteosarcoma cell line ROS 17/2.8. At concentrations between 0.1 and 10 microM, DL-propranolol specifically inhibited adenylate cyclase stimulation by the beta-adrenergic agonist isoproterenol, but did not alter either basal or PTH-stimulated activity. At these concentrations, propranolol also blunted the inhibition of alkaline phosphatase activity by isoproterenol but not PTH. Propranolol alone had minimal effects on ROS alkaline phosphatase activity at low concentrations (0.1-1 microM), but became inhibitory at high concentrations (10-100 microM). Thus, the direct effects of physiologically relevant propranolol concentrations on osteoblastic cells can be attributed principally to beta-adrenergic blockade. These findings further suggest that propranolol may enhance bone formation by preserving osteoblastic activity in the face of inhibition by beta-adrenergic agonists.
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PMID:Effects of beta-adrenergic blockade in an osteoblast-like cell line. 134 41

A monoclonal antibody raised against alkaline phosphatase (ALP) of human osteosarcoma was used to localize this enzyme in human fetal bone tissue. For light microscopy, the presence of alkaline phosphatase in osteoblasts and osteocytes was demonstrated by use of an avidin-biotin immunoperoxidase procedure. Electron microscopic immunolocalization was accomplished with an indirect immunoperoxidase method which revealed a concentration of the enzyme on matrix vesicle and osteoblast plasma membranes. In addition, many vesicular protrusions arising from areas of plasma membrane on the lateral surfaces of adjacent osteoblasts were strongly immunolabeled. Immunostaining for ALP was absent in vesicles which contained fine crystallites. Alkaline-phosphatase-rich matrix vesicles may play a significant role in the mineralization of the extracellular matrix.
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PMID:Immunolocalization of alkaline phosphatase in osteoblasts and matrix vesicles of human fetal bone. 147 98

We have constructed a series of interspecific somatic cell hybrids between the human osteoblast-like osteosarcoma, TE85, and a mouse fibrosarcoma, La-t-. In these whole-cell hybrids, we observed a 10-fold reduction of human liver/bone/kidney (L/B/K) alkaline phosphatase steady-state mRNA and alkaline phosphatase protein activity. The phenomenon of loss of tissue-specific gene expression has been termed extinction. Subclones of these hybrids were isolated, which reexpressed the alkaline phosphatase gene product. These late-passage hybrids had a reduced number of mouse fibroblast chromosomes when compared to earlier passages. This suggests that a trans-acting negative regulatory element, encoded in the fibroblast genome, regulates expression of L/B/K alkaline phosphatase. This is the first evidence that extinction plays a role in the regulation of osteoblast gene expression.
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PMID:Extinction of liver/bone/kidney alkaline phosphatase in osteosarcoma hybrid cells. 147 9

The values for serum alkaline phosphatase were evaluated in 340 patients affected with osteosarcoma of the limbs. The percentage of patients with high values for the enzyme at the onset of disease was significantly higher in the 69 cases who presented with metastases at the time of diagnosis, as compared to the 271 cases in which the neoplasm still appeared to be localized (81% vs 62%: p less than 0.001). In this last group of patients, treated with neoadjuvant chemotherapy, an evident relationship between values for alkaline phosphatase and prognosis was demonstrated. The percentage of patients who developed metastases was in fact 22% in the group with normal serum values for the enzyme at the onset of the disease and 40% for the patients with high values of the same (P less than 0.001). These data confirm the prognostic value for serum alkaline phosphatase in osteosarcoma, which should be taken into consideration when planning chemotherapy and in classifying patients for randomized therapeutic studies.
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PMID:The prognostic value of serum alkaline phosphatase in osteosarcoma of the limbs. 149 84

The phorbol ester 12-O-tetradecanoyl-13-acetate (TPA) blocked the growth of, and induced the appearance of processes in the human osteosarcoma cell line U-2 OS. The phorbol ester decreased the intracellular level of alkaline phosphatase (APase) activity (as measured per mg cell protein) and caused a marked increase in the APase activity secreted from the cells into the culture medium. The secretion of APase appeared after a lag period of 4-6 hours of TPA treatment, and it could also be visualized with histological staining. Differential ultracentrifugation of the culture media showed that the APase was released to the media in the form of vesicles. The vesicles were studied by electron microscopy and appeared similar to matrix vesicles isolated from cartilage and chondrocytes. It is thus concluded that TPA is able to induce the primary steps of mineralization in these cells.
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PMID:A phorbol ester induces secretion of alkaline phosphatase activity in human osteosarcoma cells. 152 10

A human osteosarcoma cell line, HOS TE85 cells, and a mouse osteoblastic cell line, MC3T3-E1 cells, were cultured for 3 days in a medium containing various concentrations of menaquinone-4 (vitamin K2). As a result, the proliferation of HOS cells was suppressed by vitamin K2 in a dose dependent manner up to 56% of control by 10(-7)M of vitamin K2 and that of MC3T3-E1 cells was suppressed to 84% of control by 10(-6)M of vitamin K2. Vitamin K2 increased alkaline phosphatase activity in both kinds of cells. Warfarin counteracted the effect of vitamin K2 on osteoblastic cell proliferation. Our results show that vitamin K2 modulates proliferation and function of osteoblastic cells by some mechanisms including gamma-carboxylation system.
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PMID:Vitamin K2 modulates proliferation and function of osteoblastic cells in vitro. 153 Jun 37

The Saos-2 line of human osteosarcoma cells was established in culture in 1975. These cells produce a large amount of alkaline phosphatase but little or no matrix in vitro, and are unable to grow when transplanted into athymic mice. We decided to test our local strain of Saos-2 cells for bone-inducing ability in the skeletal muscle of athymic mice by implanting freeze-dried, acetone-defatted cells, with and without a collagen carrier. A bone-inducing activity (BIA) thus was demonstrated in 88% of 90 implants of devitalized Saos-2 cells. In further studies, we have used guanidinium hydrochloride (Gu-HCl) to extract, solubilize, and remove the Saos bone-inducing agent(s) in an active state which when reprecipitated by aqueous dialysis was able to induce ultrastructurally typical endochondrial bone formation in nude mouse muscle in 92% of 48 implants. This preliminary report is offered to alert investigators to the presence of an extractable BIA in Saos-2 cells.
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PMID:Bone-inducing agent (BIA) from cultured human Saos-2 osteosarcoma cells. 153 7

A transplantable ascites-forming osteosarcoma (J. H. 1-AOS) derived from the 35th generation of spontaneous osteosarcoma, J. H. 1-OS, grown in Fischer 344 syngeneic rats was established. Tumorigenicity, histochemical and ultrastructural characteristics were investigated. Rats carrying the ascites form osteosarcoma died of cachexia about 15 days after transplantation, 1.5-2.5 x 10(6) cells/ml of tumor cells generally being involved in the ascites and tumor nodules formed in the mesentery. After inoculation into the back subcutaneous space, tumor growth was very rapid. Small round cells were detected in the Giemsa stain smear, and although osteoid formation was histologically lacking, cell surface alkaline phosphatase activity was noted both light and electron microscopically. Polyacrylamide gel electrophoresis demonstrated that alkaline phosphatase (Al-p) extracted from this tumor was consistent with Al-p from rat fetal calvaria. Thus maintenance of osteogenic potential is suggested for these ascites osteosarcoma cells, indicating their usefulness for further studies of biological behaviors of this tumor type.
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PMID:[Establishment and characterization of an ascites-forming rat osteosarcoma cell line]. 154 42

In order to characterize fibroblastic colony-forming units (CFU-F) from murine bone marrow in relation to osteogenesis, adherent cells of 7-day-old BALB/c mouse bone marrow cultures were infected with a recombinant retrovirus (N2/ delta fosB) containing the bacterial neomycin resistance gene. One of the G418-resistant clones, MN7, was selected for further analysis on the basis of its high expression of the bone-specific alkaline phosphatase. The cells have now been in culture for more than 1 year and maintain a stable phenotype. The osteogenic nature of the immortalized clone MN7 was demonstrated as follows: (1) Mineralization was detected by 85Sr uptake and with the Von Kossa staining method only after in vitro cultivation on a collagen type I matrix. (2) Osteoblastic phenotype markers, including the synthesis of type I collagen, osteonectin, and the bone-specific isoenzyme of alkaline phosphatase were expressed in vitro. (3) MN7 cells responded to bone effectors such as parathyroid hormone and 1,25-dihydroxyvitamin D3. (4) Intraperitoneal injection of MN7 cells into 1-day-old BALB/c mice produced typical osteosarcomas in all animals. We conclude that MN7, derived entirely in vitro from a stromal CFU-F colony, represents a stable murine osteosarcoma cell line expressing the osteoblastic phenotype and provides the first direct evidence needed to establish adult mouse marrow-derived, nonhematopoietic stromal cells as osteoprogenitors.
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PMID:Establishment of an osteogenic cell line derived from adult mouse bone marrow stroma by use of a recombinant retrovirus. 157 49

Recent studies have demonstrated the presence of estrogen receptor (ER) in both normal human osteoblast-like and osteoblast-like osteosarcoma cells. The number of ER in cultured osteoblastic cells is very low (200-500 sites/cell). This has complicated characterization of the biological role of estrogens in bone cells. To study the responsiveness of bone cells to estrogens, we established osteoblast-like cell lines expressing higher ER levels. ROS 17/2.8, an osteoblastic cell line, was stably transfected with the cDNA encoding for the mouse ER. After a selection period, positive clones were isolated and evaluated for the presence of ER by both Northern blot analysis and ligand binding assays. Using these techniques, we detected a significant increase in the level of both ER transcript and binding compared to that in wild-type cells. The levels of expressed ER protein were similar to those reported in normal human osteoblast-like cells in primary culture (approximately 2000 sites/cell). To test whether the exogenously inserted ER was responsive, both wild-type and ER stably transfected cells were transiently transfected with a reporter construct containing an estrogen-responsive element linked to a truncated thymidine kinase promoter and a chloramphenicol acetyltransferase (CAT) reporter gene. Exposure of the cells to increased concentrations of estradiol induced a slight increase in CAT activity in wild-type cells (approximately 1.5-fold) at maximal stimulation; however, it provoked a clear concentration-dependent increase in CAT activity in the ER stably transfected cells, with a maximal stimulation of approximately 10-fold. This event was receptor mediated, since ICI 164,384, an ER antagonist, blocked the enhancement of estradiol-induced CAT activity, and it was specific, since other steroid hormones did not stimulate CAT activity. Finally, we evaluated the ability of ER to modulate an endogenous estrogen-responsive gene by measuring the activity of the enzyme alkaline phosphatase. In addition, diethylstilbestrol, a synthetic estrogen agonist, increased the activity of both the CAT reporter gene and the endogenous alkaline phosphatase enzyme. In summary, we have established osteoblast-like cells expressing high levels of an exogenously inserted ER, which has characteristics similar to those of the endogenous ER in terms of its Kd. Finally, the exogenous ER regulates both exogenously inserted construct (VITERECAT) and endogenous properties of the cells (enzymatic activity and proliferation).
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PMID:Estrogens modulate the responsiveness of osteoblast-like cells (ROS 17/2.8) stably transfected with estrogen receptor. 157 85


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