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Query: DrugBank:APRD00249 (Mutagen)
 5,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Marrow stroma has been shown to have osteogenic potential. Here we report the characterization of a unique stromal cell line derived from mouse bone marrow (MBA-15), which expresses osteoblastic phenotype in vitro and forms bone in vivo. More than 70% of cells in culture were histochemically positive for alkaline phosphatase. The enzyme levels were enhanced threefold when cultures were treated with dexamethasone. Gel electrophoresis of [3H]-proline-labeled cultures showed that MBA-15 cells produced only type I collagen. These cells were responsive to PTH, as indicated by a 50-fold increase in intracellular cAMP. Prostaglandin E2, but not calcitonin, stimulated cAMP up to 70-fold. When cultures were grown to confluence and fed daily with ascorbic acid and beta-glycerophosphate, the cells formed a Von Kossa positive, thick extracellular matrix, shown to contain hydroxyapatite crystals. MBA-15 cells produced mineralized bone when implanted in diffusion chambers. These results indicate that the MBA-15 cell line possesses osteoblastic features in vitro and osteogenic capacity in vivo.
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PMID:Bone marrow-derived stromal cell line expressing osteoblastic phenotype in vitro and osteogenic capacity in vivo. 254 12

The effects of retinoic acid (RA) on the expression of osteoblastic-related cell markers was examined. A marrow stromal osteogenic cell line, MBA-15, was analyzed by Northern blotting for the expression of bone matrix proteins. These cells constitutively express mRNA encoding for procollagen alpha 2 (I), osteonectin, osteopontin, biglycan, and alkaline phosphatase (ALK-P). Gene expression was unchanged in response to RA triggering for 24 hr. Furthermore, cell growth and enzymatic activities of ALK-P and neutral endopeptidase (CD10/NEP) were studied. These parameters were examined in MBA-15 and clonal populations representing different stages of differentiation. The cell's growth rate was unchanged, while ALK-P activity was greatly increased during the culture period under RA treatment in MBA-15 and in the clonal cell lines examined while CD10/NEP activity displayed a different pattern. MBA-15.4, a preosteoblast cell line, exhibited an inhibition in CD10/NEP activity at the beginning of the culture period, reaching basal level with time. This activity was greatly increased over control level in MBA-15.6, a mature stage of osteoblasts. Furthermore, the response of cell lines to various growth factors was tested subsequent to priming the cultures with RA. A synergistic effect was monitored for ALK-P activity in MBA-15.4 and MBA-15.6 cells under rh-bone morphogenic protein (BMP-2) and purified osteogenin (BMP-3), and an antagonist effect was measured when cells were exposed to transforming growth factor beta (TGF beta). Contrarily, BMP-2 and BMP-3 inhibited the CD10/NEP activity that had remained unchanged following priming of the cell with RA. Insulin-like growth factor I (IGF-I) and basic fibroblast growth factors (bFGF) did not affect either ALK-P nor CD10/NEP activities in both cloned cells. Cellular response to bone-seeking hormone, parathyroid hormone (PTH), and prostaglandin E2 (PGE2) was monitored by activation of intracellular cAMP. Treatment with RA caused a dramatic decrease in MBA-15.6 cell responses to PTH and PGE2, but no significant effects could be observed in other clonal lines.
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PMID:Differential effects of retinoic acid and growth factors on osteoblastic markers and CD10/NEP activity in stromal-derived osteoblasts. 752 53

The functional modulation of enzymatic activities of alkaline phosphatase (ALK-P) and neutral endopeptidase (CD10/NEP) in MBA-15.4 and MBA-15.6 marrow stromal osteoblastic cells was studied. The hormonal effects of parathyroid hormone (PTH) and 1,25 (OH)2D3 combined with various growth factors (bone morphogenic protein [BMP-2 and BMP-3], TGF beta and IGF-I) on these cells were monitored. The cell responses of MBA-15.4, a preosteoblastic cell, and MBA-15.6, a more mature osteoblastic cell, to the growth factors and the hormonal challenge were measured by changes of the enzymatic activities (ALK-P and CD10/NEP). The cellular response was not uniform and revealed a differential pattern.
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PMID:PTH and 1,25(OH)2 vitamin D priming to growth factors differentially regulates the osteoblastic markers in MBA-15 clonal subpopulations. 774 41

The present study describes a new three-dimensional (3-D) culture system that enables the maintenance and phenotypic expression of bone marrow stromal osteoblasts. This culture substratum is advantageous in that it provides suitable conditions for attachment, growth, and differentiation of cells forming 3-D layers. The MBA-15 cell line was grown in unlimited quantities on 3-D Fibro-Cel carriers. These cells mineralized when exposed to ascorbic acid and beta-glycerophosphate (beta GP). Under these mineralization conditions, mRNA expressions of procollagen alpha 2(I) and [3H]-proline-labeled protein were increased. The expression of mRNA for osteonectin and to a lesser extent, for osteopontin was increased, whereas alkaline phosphatase and biglycan remained unaffected under similar conditions. Exposure of mineralizing cultures to dexamethasone reduced mRNA of procollagen alpha 2 (I) and osteonectin to control level. Scanning electron microscopy revealed that cells were grown along the fabric's fibers and produced collagen fibrils. Under appropriate conditions, extensive mineralization had taken place. The mineralization process involves the formation of calcospherites, and correlates with an increase in calcium content. The Fibro-Cel carriers enable formation of 3-D architecture and mineralized tissue in vitro.
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PMID:Mineralization of marrow-stromal osteoblasts MBA-15 on three-dimensional carriers. 795 77

This report documents characterization of five osteogenic cell subpopulations of bone marrow stroma. The clonally derived cell lines were isolated from the parental line MBA-15 known to express osteoblastic-associated features in vitro and to form bone in vivo. The latter, presumably "arrested" at a particular stage along the osteogenic lineage, are useful models to study the processes involved in the differentiation of bone forming cells. The clones differ in their morphology, proliferation rate, quantities and distribution of extracellular matrix proteins, levels of alkaline phosphatase activity and activation of adenylate cyclase by parathyroid hormone and/or prostaglandin E. These properties have been retained during prolonged growth and subculturing through many passages. MBA-15.4 is a presumptive preosteoblast with a fibroblast-like appearance; it proliferates rapidly, synthesizes equal amounts of collagen and noncollagenous proteins, and produces constitutively low levels of alkaline phosphatase. This clone has PGE2-stimulated adenylate cyclase activity and a very low constitutive response to PTH. On the other hand, MBA-15.6 has a large polygonal morphology with limited proliferative potential, synthesizes twice as much noncollagenous proteins as collagen, has high alkaline phosphatase activity, and responds strongly to PTH. The characteristics of the other clones place them between these two categories. The effects of 10(-7) M dexamethasone or 10(-12)-10(-8) M 1,25 dihydroxyvitamin D3 on growth and differentiation further strengthen the variance between these clones. The different in vitro characteristics of the various clones were directly reflected in their bone formation ability in vivo. When transplanted under the renal capsule, MBA-15.33 formed a thick fibrous tissue, MBA-15.4 formed small foci of bone, and MBA-15.6 formed massive woven bone at the same period of time.
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PMID:Marrow stroma-derived osteogenic clonal cell lines: putative stages in osteoblastic differentiation. 838 1

MBA-15, a marrow stromal-derived cell line, was shown to express an estrogen receptor. This finding was confirmed by in situ hybridization and receptor binding assay. An exposure to estrogen (10(-12)-10(-6) M) in a dose response manner resulted in a decrease of cell proliferation as measured by MTT assay. Cell function was measured by enzymatic activities of two osteoblastic markers, CD10/NEP and alkaline phosphatase. These enzymatic activities were elevated following the estrogen treatment. This model enabled direct evaluation of the estrogen effect on stromal osteoblast cells.
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PMID:The expression of estrogen receptor and estrogen effect in MBA-15 marrow stromal osteoblasts. 885 24

The clonal subtypes of cells in the osteogenic family represented by fibroblastoid MBA-15.33, preosteoblast MBA-15.4, and mature osteoblastic MBA-15.6 cells were used to study the effects of glucocorticoid (dexamethasone). The role of dexamethasone was monitored on cell attachment when plated on various protein substrata (BSA, collagen 1, and Matrigel). A 24 h exposure of the cells to 10(-6) M or 10(-7) M dexamethasone differential affects their attachment preference. MBA-15.33 and MBA-15.4 cells increased their attachment capability on collagen 1, while MBA-15.6 cells' attachment was inhibited. Pretreatment with (10(-6) M) dexamethasone caused an increase in attachment on Matrigel by MBA-15.33 cells and to less extent by MBA-15.4 cells. Additionally, measurements of two enzymatic activities were monitored; one is alkaline phosphatase (ALK-P), and the second is neutral endopeptidase (CD10/NEP). MBA-15.33, MBA-15.4, and MBA-15.6 cells were exposed to dexamethasone or to various growth factors (bone morphogenic protein (BMP-2 and BMP-3), TGF beta, and IGF-1). In some experiments, pretreatment of cells by dexamethasone was followed by exposure to the growth factors. The cells' challenged cellular responses were not uniform and revealed a differential pattern when their ALK-P and CD10/NEP enzymatic activities were measured.
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PMID:Dexamethasone regulation of marrow stromal-derived osteoblastic cells. 889 93

Our aim was to study the role of various extracellular matrices (ECM) on growth and differentiation of marrow stromal cells in vitro. Morphology changes, gene expression, and enzymatic activities were monitored in stromal osteoblastic MBA-15 and adipocytic 14F1.1 cells. These stromal cells were plated on dishes precoated with different substrata, such as matrigel (basement membrane), collagen type I, and endothelial ECM, and compared with cells plated on protein-free dishes. Striking morphological differences were observed when the cells grew on these different substrata. Changes in cell shape and growth also led to differential mRNA expression and enzymatic activities. When MBA-15 cells were plated on collagen, there was a decrease in mRNA for alkaline phosphatase (ALK-P), osteopontin (OP), and osteonectin (ON), and an increase in mRNA for procollagen (I). A differential effect was noted on 14F1.1 cells, the mRNA for ALK-P increased, the expressions of OP and ON lowered, and no expression for procollagen (I) was monitored. MBA-15 cells cultured on matrigel had decreased mRNA for ALK-P and OP, while they had increased ON mRNA expression and remained unchanged for procollagen I. No change in mRNA expression by 14F1.1 cells was monitored when cultured on matrigel. Functional enzymatic activities of ALK-P markedly decreased in MBA-15 cells cultured on various substrata, and increased or were unchanged in 14F1.1 cells. An additional enzyme, neutral endopeptidase (CD10/NEP), altered differentially in both cell types; this enzymatic activity increased or was unchanged when cells were cultured on these matrices. The results indicate a specific role for different ECM on various stromal cell types and their function.
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PMID:Phenotypic expression of marrow cells when grown on various substrata. 917 88

MBA-1, a bone marrow stroma-derived cell line, was transplanted in an ectopic site and formed endochondral bone. The ossicle developed through stages of cell proliferation, differentiated into a zone of hypertrophy and formed a chondroid-like area which further developed to primary mineralized bone. We explored the expression of various matrix proteins by MBA-1 cells in vitro and in the ossicle formed in vivo. MBA-1 cells constitutively expressed mRNAs encoding for collagen I, non-collagenous proteins and alkaline phosphatase. RNA extracted from the ossicle formed by these cells was expressed in a different pattern. The in vivo maturation of MBA-1 cells was accompanied by low expression of mRNA for procollagen alpha 2(I) and a marked increase in osteonectin and osteopontin mRNA levels. Thus, the ability to follow expression of these genes through bone formation in vivo has been demonstrated.
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PMID:Bone-related matrix proteins expression in vitro and in vivo by marrow stromal cell line. 943 44

Three sows were fed a diet mixed with Fusarium moniliforme fungal culture from the 107th day of pregnancy until parturition. Fumonisin B(1) toxin was administered to two sows (sows 1 and 2) in a daily dose of 300 mg for an additional 7 days subsequent to parturition, i.e., for a total of 14-16 days. The third sow (No. 3) was given the toxin in the same daily dose only until parturition, i.e., for 7 days in total. There were no symptoms observed in any of the sows. Two piglets were taken from each of the three sows and sacrificed immediately after parturition, i.e., prior to the first suckling. After 24 h, two additional piglets were taken for slaughter from each of the litters, which by then had access to colostrum. Finally, on the 7th day postparturition another two piglets per litter were sacrificed and material obtained from them was processed for examination. It was established that fumonisin B(1) present in the Fusarium moniliforme culture resulted in damage to the fetuses in utero. Of the changes indicating toxic effect, intraalveolar, subpleural, and interstitial pulmonary edema of various degrees of severity could be detected in the piglets sacrificed immediately following parturition and before the first suckling. Pathological changes were observed in the histopathological sections of the liver, and increases in the activities of plasma aspartic acid transaminase (AST), gamma glutamyl transferase (GGT) and alkaline phosphatase (AKLP), higher than physiological levels were detected. The serum-free sphinganine/sphingosine ratio, considered a bioindicator of fumonisin B(1) toxicosis, varied in accordance with the degree of severity of the changes which occurred. The values obtained were found to be between 0.29 and 0.36 in the cases of severe pulmonary edema, and between 0.20 and 0.24 for the cases of mild pulmonary edema. In the piglets of the sows fed the toxin for an additional 7 days subsequent to parturition and which were born with severe pulmonary edema, mild pulmonary edema could be detected after colostrum suckling, 24 h, and 7 days after parturition. The SA/SO value of the serum in these two piglets was 0.19 and 0.20, while at the same time AST, GGT, and ALKP values higher than physiological levels were measured. In the milk samples taken from sows 1 and 2 and examined after 24 h and after 7 days FB(1) was detected in quantities of 18.0-27.5 ppb. There were no changes observed on the seventh day in the piglets of the third sow, the diet of which contained no toxin after parturition. However, as the piglets of the third sow demonstrated only mild effects of pulmonary edema it is not possible to establish with certainty a postpartum cause-effect relationship between fumonisin in colostrum and pulmonary edema.
Teratog Carcinog Mutagen 2000
PMID:Preliminary communication: examination of the harmful effect to fetuses of fumonisin B(1) in pregnant sows. 1099 76


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