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: EC:3.1.3.1 (alkaline phosphatase)
47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A newly established human osteosarcoma cell line, HS-Os-1, from an osteoblastic tumor arising in the left humerus of an 11-year-old girl was morphologically characterized in vitro and in vivo. HS-Os-1 cells in a monolayer have been maintained for more than 2 years since the initial cultivation, and were round or polygonal in shape with marked pleomorphism. Their cytoplasm was strongly positive for specific markers of osteoblasts, such as alkaline phosphatase and osteocalcin. Tumors induced in nude mice by HS-Os-1 cell inoculation at passage 12 or 23 revealed typical histological features of osteoblastic osteosarcoma, similar to those observed in the original tumor, producing prominent osteoid matrix with calcification. Ultrastructurally, HS-Os-1 cells in vitro and tumor cells in vivo showed similar well-developed, markedly dilated rough endoplasmic reticulum, polysomes and microfilaments in their cytoplasm. Additionally, many collagen fibers associated with deposition of electron-dense material were detected in the stroma featuring osteoid matrix. Thus, the HS-Os-1 cell line was shown to exhibit its osteoblastic nature in vitro and in vivo, and therefore might become an extremely useful tool for various pathomorphological investigations on human osteosarcomas.
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PMID:Morphological characterization of a newly established human osteosarcoma cell line, HS-Os-1, revealing its distinct osteoblastic nature. 167 69

We examined the effect of nicotine on cellular proliferation, as measured by [3H]thymidine (TdR) incorporation and cell count, and on alkaline phosphatase activity in UMR 106-01 rat osteoblastic osteosarcoma cells. The cells were cultured with varying concentrations of nicotine in serum-free medium for 2 to 72 hours. Nicotine produced a dose-dependent suppression of TdR incorporation, with maximum suppression seen at 10 mM (7% of control); the EC50 for suppression of TdR incorporation was 10 microM. 1 microM nicotine decreased cell number by 20% to 30%. The time course of the effect of 100 microM nicotine on DNA synthesis was measured by TdR incorporation. TdR uptake was measured at 2, 4, 6, 24, 48, and 72 hours. After the addition of nicotine, the following biphasic response in TdR incorporation was observed: a 15% decrease at 2 hours, recovery to near control value at 6 hours, a 27% decrease by 24 hours, and a maximum decrease of 88% by 48 hours. Over a dose range of 1 nM to 10 mM, nicotine produced a dose-dependent increase in alkaline phosphatase activity with maximum stimulation seen at 1 microM (189% of control). We conclude that nicotine suppresses cellular proliferation and stimulates alkaline phosphatase activity in UMR 106-01 osteoblast-like cells. These results may be of significance in the development of osteoporosis and alveolar bone loss associated with the use of tobacco.
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PMID:Effects of nicotine on cellular function in UMR 106-01 osteoblast-like cells. 179 80

High levels of interleukin-6 (IL-6) have been detected in synovial fluid from patients with inflammatory arthropathies associated with local bone resorption, suggesting a role for IL-6 as a local regulator of bone resorption and remodeling. In the present study we examined the effects of IL-6 on [3H]thymidine ([3H]TdR) incorporation, collagen synthesis, and alkaline phosphatase activity in UMR-106-01 rat osteoblastic osteosarcoma cells. IL-6 stimulated a dose-dependent increase in [3H]TdR incorporation that was maximal at 1000 U/ml (-147% of basal, p less than 0.005) in osteoblastlike cells that were in a logarithmic phase of growth. The increase in [3H]TdR incorporation was maximal between 12 and 24 h and was neutralized by pretreatment with the polyclonal rabbit antibody to IL-6. IL-6 also increased cell number and the secretion of prostaglandin E2 in UMR-106-01 cells in logarithmic growth phase. The stimulation of [3H]TdR incorporation and release of PGE2 into the culture medium by IL-6 was inhibited by indomethacin. A 24 h exposure of the osteoblastlike cells to 1000 U/ml of IL-6 reduced [3H]proline incorporation into collagenase-digestible (CDP) protein to 73% of control values (p less than 0.01). Noncollagen protein (NCP) synthesis was inhibited to 80% of control values (p less than 0.01) by 1000 U/ml of IL-6. The inhibitory effect was relatively greater on CDP than on NCP and consequently resulted in a decrease in the percentage of collagen synthesis. Alkaline phosphatase activity was not altered in these cells after a 24 h exposure to 1-1000 U/ml of IL-6.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of interleukin-6 on cellular function in UMR-106-01 osteoblastlike cells. 202 35

A new human cell line, HS-Os-1, derived from a case of osteoblastic osteosarcoma arising in the humerus of an 11-year-old girl was established. Light microscopically, HS-Os-1 cells growing in a monolayer (in vitro) were pleomorphic, intermingled with a few multinucleated giant ones, and positive with alkaline phosphatase reaction. In the transplanted tumors in athymic nude mice (in vivo), atypical spindle or polygonal cells densely proliferated with prominent osteoid formation and even calcification. HS-Os-1 cells, both in vitro and in vivo, were mostly positive for vimentin and a few for S-100 protein. Ultrastructurally, HS-Os-1 cells in vitro and in vivo also revealed essentially the same features as the eccentrically located, euchromatin-rich nuclei with prominent nucleoli, a lot of well-developed, irregularly-dilated rough endoplasmic reticula, polysomes and microfilaments in the cytoplasm. Namely, HS-Os-1 cells fully expressed and possessed morphological characteristics as osteoblastic nature during the cultivation and heterotransplantation. This cell line, therefore, proved to be extremely useful to search for human osteosarcomas.
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PMID:[Establishment and characterization of a cell line, HS-Os-1 derived from an osteoblastic type of human osteosarcoma]. 208 79

Inadequate vitamin D intake is an important cofactor in clinical and experimental bone disease induced by chronic cadmium exposure. The interaction was investigated by culture of rat osteoblastic osteosarcoma cells (ROS 17/2.8) in a serum-free medium with equimolar concentrations of cadmium chloride and 1 alpha,25-(OH)2 vitamin D3. After addition of cadmium alone to culture medium, the unstimulated secretion of osteocalcin and cellular alkaline phosphatase activity were inhibited at 10 pM, and of DNA synthesis and proline incorporation into collagen at 500 nM. In the presence of equimolar amounts of cadmium and 1 alpha,25-(OH)2 vitamin D3, all four responses paralleled those of 1 alpha,25-(OH)2 vitamin D3 alone up to the inhibitory concentration of 500 nM cadmium. Neither 10 nM 1 alpha,25-(OH)2 vitamin D3 nor 1 microM cadmium induced synthesis of metallothionein in these cells indicating that the protective effect of D3 was not related to the induction of a metallothionein-like protein in ROS 17/2.8 cells. In the presence or absence of D3, cadmium inhibited osteoblastic function at concentrations below the whole-organ concentration of cadmium in bone as reported in experimental and clinical cadmium-induced osteotoxicity. The extreme sensitivity of ROS 17/2.8 cells to cadmium may relate to the absence of metallothionein synthesis.
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PMID:Toxicity of cadmium to rat osteosarcoma cells (ROS 17/2.8): protective effect of 1 alpha,25-dihydroxyvitamin D3. 231 24

Recent studies have suggested that interleukin-1 or tumor necrosis factor-stimulated bone resorption is mediated by osteoclast-activating factor elaborated by osteoblastic cells. Since recombinant interferon gamma inhibits stimulation of bone resorption by these cytokines, we examined here the effects of recombinant human interferon gamma (rhIFN-G) on DNA synthesis and alkaline phosphatase (ALP) activity of a human osteoblastic osteosarcoma cell line, SaOS2, under preconfluent culture conditions. Addition of rhIFN-G to the cells markedly inhibited their DNA synthesis and ALP activity in a dose-dependent fashion. However, the inhibition was not dependent on the culture time. The highest inhibitory effect was observed in 10% serum-containing culture medium. The inhibitory effect on DNA synthesis was not eliminated by addition of indomethacin, a cyclooxygenase inhibitor. Furthermore, combination of rhIFN-G and recombinant human tumor necrosis factor alpha inhibited their DNA synthesis and the ALP activity in synergistic fashion. Therefore, these data suggest that rhIFN-G is a potent inhibitor for human osteoblastic cells.
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PMID:[Inhibitory effect of recombinant human interferon gamma on human osteoblastic osteosarcoma cells (SaOS2)]. 251 49

1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) significantly stimulated cellular alkaline phosphatase activity in a human osteoblastic osteosarcoma cell line (TE-85 cells) in serum-free medium with 0.1% bovine serum albumin as the hormone carrier in a dose- and a time-dependent manner. The extent of the maximal stimulation was greater and the minimal dose that was required for stimulation was lower than those previously reported for TE-85 cells in the presence of serum. The magnitude of the stimulation of alkaline phosphatase activity by 1,25(OH)2D3 varied with the cell density. Daily changes of conditioned medium, as compared with no medium changes, significantly reduced the magnitude of the stimulation, suggesting that endogenous factors secreted into culture medium could play an enhancing role. Finally, application of Northern blot analysis using an oligodeoxynucleotide probe corresponding to a unique sequence of the human bone/liver/kidney alkaline phosphatase cDNA coding region revealed that 1,25(OH)2D3 increased the alkaline phosphatase mRNA level, suggesting that the increase in alkaline phosphatase activity was a result of either an increase in the rate of transcription or an increase in message stability.
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PMID:Stimulation of cellular alkaline phosphatase activity and its messenger RNA level in a human osteosarcoma cell line by 1,25-dihydroxyvitamin D3. 259 47

Cells of the dental papilla are capable of odontoblastic, fibroblastic, and endothelial differentiation and formation of dentin and the dental pulp. In the present study dental papilla cells, obtained from human tooth buds (HDP cells), were cultured in vitro through 3 to 7 passages. After exposure to prostaglandin E2 there was a marked decrease in intracellular cyclic AMP (cAMP) levels as compared to hormone-free controls. Parathyroid hormone and calcitonin had stimulatory effects with 1 and 2 log increases in cAMP, respectively. The HDP cells showed moderate activity of alkaline phosphatase, 1 log higher than that of hamster kidney fibroblasts (BHK 13) and 1 log lower than that of osteoblastic osteosarcoma cells (ROS 17/2). When cultured for 4 or 8 wk in diffusion chambers (DC) implanted in athymic mice, many of the HDP cells underwent odontoblastic morphodifferentiation with very long, single processes extending into the matrix. This matrix contained banded and unbanded collagen fibers. Neither light nor electron microscopy of the DC content revealed mineral deposits. These results suggest that HDP cells have an intrinsic potential for partial odontoblastic differentiation; inductive signals like those originating from odontogenic epithelium are probably essential for the completion of hard tissue formation.
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PMID:Hormone-responsive cells derived from human dental papilla: characterization in vitro and in vivo in diffusion chambers. 302 24

Transforming growth factor-beta (TGF beta), a polypeptide that controls growth and differentiation in many cell types and has recently been found in abundant amounts in bone, was examined for its effects on cells with the osteoblast phenotype using the clonal osteoblastic osteosarcoma cell line ROS 17/2.8. TGF beta increased alkaline phosphatase (AP) activity and the rate of collagen synthesis per cell. Cell proliferation was inhibited, and the morphological appearance of the cells was markedly changed. All effects were observed at concentrations as low as 0.1 ng/ml TGF beta. Increases in AP activity were detectable after 24 h and increased progressively with time. TGF beta increased AP activity under serum-free conditions and during thymidine-induced inhibition of DNA synthesis. The increase in AP activity mediated by TGF beta could be completely inhibited with actinomycin D and cycloheximide. 1,25-Dihydroxyvitamin D3 at 10(-7) M slightly increased AP activity in ROS 17/2.8 cells, but strongly inhibited AP activity when the cells were pretreated with TGF beta. The data suggest that TGF beta stimulates expression of the osteoblastic phenotype in ROS 17/2.8 cells and that TGF beta may be an important regulator of local bone remodeling.
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PMID:Effects of transforming growth factor-beta on osteoblastic osteosarcoma cells. 347 42

Human osteosarcoma specimens were sliced in a cryomicrotome under strict morphological guidance. Serial sections of ten 10 micron slices each were collected in two groups according to morphologic criteria, one containing mostly undifferentiated tumor tissue, the other predominantly well-differentiated tumor tissue. The two series were analysed chemically for alkaline phosphatase (APase) acid phosphatase (acPase), beta-glucuronidase and proteolytic activities; protein, phosphorus, hydroxyproline, hexosamine, water and collagen contents were also determined. Four different types of osteosarcoma were studied: case 1 was a highly malignant osteoblastic osteosarcoma, case 2 a small cell sclerosing osteosarcoma case 3 a well-differentiated osteosarcoma, and case 4 a highly malignant anaplastic osteosarcoma. The types of cases 1, 2 and 3 are known as osteoid-forming tumors. In their less well differentiated areas APase activity was about twice as high as in better differentiated osteosarcoma. In contrast, no APase was found in the wholly undifferentiated areas of case 4, while the enzyme showed a marked increase in the areas of incipient differentiation of this tumor. The matrix of tumors differs with regard to collagen and hexosamine contents, in accordance with the general state of differentiation. In general, increasing hexosamine contents together with decreasing hydroxyproline contents will reflect the anaplastic, dedifferentiated osteosarcoma. Calcification evident in the better differentiated areas of osteosarcoma is indicated by the phosphorus content, highest in case 2, with cases 3, 1, and 4 following in sequential order.
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PMID:Biological characterization of human bone tumors. V. Zonal characterization of osteosarcoma: topological biochemical analysis correlated with morphology. 390 6


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