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)

The effects of PTH and calcitonin (CT) on the expression of mineralization-related phenotypes by chondrocytes were examined. In cultures of pelleted growth-plate chondrocytes. PTH caused 60-90% decreases in alkaline phosphatase activity, the incorporation of 45Ca into insoluble material, and the calcium content during the post-mitotic stage. These effects of PTH were dose-dependent and reversible. In contrast, CT increased alkaline phosphatase activity, 45Ca incorporation into insoluble material, and the calcium content by 1.4- to 1.8-fold. These observations suggest that PTH directly inhibits the expression of the mineralization-related phenotypes by growth-plate chondrocytes, and that CT has the opposite effects.
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PMID:Effects of parathyroid hormone and calcitonin on alkaline phosphatase activity and matrix calcification in rabbit growth-plate chondrocyte cultures. 236 69

Fourteen patients undergoing periodic dialysis who had been taking AL(OH)3 as an intestinal chelant of phosphorus have been examined. AL(OH)3 was replaced by CaCO3 for a period of 6 months. At the end of the study, statistically significant reductions were evidenced in alkaline phosphatase, basal serum aluminiaemia and its increase after Desferal test, while the bicarbonates (HCO3) were found to be increased. Statistically non-significant increases were observed in calcaemia, PTH, and pH. It is concluded that the replacement of AL(OH)3 with CaCO3 is effective in controlling phosphoraemia, in diminishing serum concentrations and tissue deposits of Al and in improving uraemic acidosis.
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PMID:[Use of calcium carbonate as an intestinal chelator of phosphorus]. 238 24

Human osteoblast cultures derived as out-growths from trabecular bone released tumor necrosis factor (TNF alpha) upon stimulation of the cells with human recombinant interleukin 1 (IL1; 10(-13)-10(-11) M), human recombinant granulocyte-macrophage colony-stimulating factor (100-1000 U/ml), and bacterial lipopolysaccharide (5-500 ng/ml). The osteotropic hormones 1,25-dihydroxyvitamin D3, PTH, and calcitonin had no effect on TNF production. The TNF released by the osteoblasts was identified as TNF alpha, using a specific anti-TNF alpha monoclonal antibody to neutralize its activity. Immunohistochemical staining of the cells using the same antibody revealed that all of the cells in the cultures were capable of producing TNF alpha, including those that also expressed alkaline phosphatase activity. Immunoreactive protein could be detected in the perinuclear region when cells were cultured in the presence of monensin, suggesting accumulation of newly synthesised protein in the Golgi apparatus. These results suggest that human osteoblasts, which have been shown previously to respond to TNF alpha, can synthesize and release TNF in response to IL1 and granulocyte-macrophage colony-stimulating factor. TNF may, therefore, not only have a pathological role in conditions of chronic inflammation, but also may act as a local paracrine or autocrine regulator of osteoblast function.
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PMID:Production of tumor necrosis factor by human osteoblasts is modulated by other cytokines, but not by osteotropic hormones. 240 45

Human osteoblast-like cells were examined for the presence of the Ca2+-Mg2+ ATPase pump. The osteoblast-like cells had characteristic features of the osteoblast phenotype, including the presence of osteonectin, bone GLA protein, and type I collagen. The cells were able to mineralize matrix, their production of cAMP increased in response to PTH, and their alkaline phosphatase activity increased in response to 1,25-dihydroxyvitamin D3. Immunocytochemical staining of the osteoblast-like cells with a monoclonal antibody against human red cell Ca2+-Mg2+ ATPase demonstrated the presence of an epitope of the Ca2+-Mg2+ ATPase in these cells; staining of paraffin-embedded osteoblast-like cell sections demonstrated anti-Ca2+-Mg2+ ATPase staining only in cell plasma membranes. Western blot analysis of osteoblast-like cell homogenates showed that the monoclonal antibody to human erythrocyte Ca2+-Mg2+ ATPase bound to a major band at 140,000 mol wt, similar to the mol wt of known plasma membrane Ca2+-Mg2+ ATPases. The presence in the osteoblast-like cells of a Ca2+-Mg2+ ATPase similar to the human red cell calcium pump suggests that this enzyme may play a role in osteoblast intracellular calcium homeostasis.
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PMID:Epitopes of the human erythrocyte Ca2+-Mg2+ ATPase pump in human osteoblast-like cell plasma membranes. 246 88

The effect of synthetic human parathyroid hormone (hPTH) on the formation of matrix vesicles (MV), and on the rate of cell division, production of cellular alkaline phosphatase (AP) and protein by primary cultures of chicken epiphyseal growth plate hypertrophic chondrocytes was investigated. Addition to serum-containing or serum-free media of physiological levels of hPTH, in a range from 0.1 to 10 nM, caused a progressive decrease in the formation of AP-rich MV. However, studies on incorporation of [3H]choline into MV indicate that MV formation per se was not significantly decreased. hPTH was found to markedly decrease the expression of cellular AP, accompanied by an increase in cell division [( 3H]thymidine incorporation) and protein synthesis. Since these effects of hPTH were augmented by 3-isobutyl-1-methylxanthine (IBMX), a phosphodiesterase inhibitor, and mimicked by the cAMP analogue N6,O2'-dibutyryl-adenosine 3',5'-cyclic-monophosphate (DBcAMP), the findings clearly indicate that hPTH was acting through the classic cAMP-mediated mechanism. Inasmuch as elevation of AP in growth plate chondrocytes coincides with MV formation, maturation and hypertrophy of the cells, and induction of mineralization, the stimulation of cell division and suppression of cellular AP indicates that hPTH would cause the cells to revert to a less differentiated state. Thus, elevation in PTH, which results from lowered circulating levels of Ca2+, should inhibit mineral deposition in the growth plate. This may be a physiological protective mechanism to prevent a further drain on serum Ca2+.
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PMID:Effect of synthetic human parathyroid hormone on the levels of alkaline phosphatase activity and formation of alkaline phosphatase-rich matrix vesicles by primary cultures of chicken epiphyseal growth plate chondrocytes. 246 54

Two new bone cell lines were established by immortalizing cells derived from embryonic rat calvariae with a recombinant retrovirus containing the cDNA for SV-40 large T antigen and the neomycin resistance gene. One cell line, RCT-1, isolated from early digest cells, a population which typically does not express osteoblastic features, displayed osteoblastic characteristics only after 3 days of treatment with 1 microM retinoic acid: alkaline phosphatase activity increased from 0.003 to 0.25 mumol/min.mg protein, the steady state level of type I procollagen mRNA increased 4-fold, and the cells acquired a PTH-stimulatable adenylate cyclase (EC50, 10 nM). mRNA for osteopontin, an abundant bone matrix protein, was induced in RCT-1 cells by 1,25-dihydroxyvitamin D3 (10 nM). The second cell line, RCT-3, isolated from late digest cells, a population previously shown to be enriched with differentiated osteoblasts, expressed constitutively the properties described above. In addition, RCT-3 cells responded to interleukin-1 by increased prostaglandin production (EC50, 20 pM) and to prostaglandin E2 by enhanced cAMP accumulation, features exhibited by calvarial cells in organ culture. Thus, the SV-40 immortalized cell lines we describe retained many of the characteristics of osteoblasts in primary culture, including hormonal regulation of phenotype-related genes. In RCT-1 cells the coordinate induction of several properties by retinoic acid offers a new model for the study of differentiation-related gene expression in bone cells.
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PMID:Rat calvarial cell lines immortalized with SV-40 large T antigen: constitutive and retinoic acid-inducible expression of osteoblastic features. 247 May 84

In 40 patients (17 male, 23 female, median age 57 years) with the presumptive diagnosis of primary (essential) thrombocythemia (PTH) according to the diagnostic requirements of the Polycythemia-Vera-Study-Group (PVSG) a follow-up study and a histological evaluation of initial trephine biopsies of the bone marrow were performed. Thorough review of the hematological data during the lengthy course of disease (observation time ranging from 1.5-10.5 years) and the histomorphology of the bone marrow implied a discrimination into two groups of patients. Group I patients (n = 26; 10 male, 16 female) were compatible with PTH according to our follow-up studies. Group II patients consisted of 14 cases (7 male, 7 female) which suggested retrospectively early hyperplastic stages of agnogenic myeloid metaplasia (AMM) with concomitant thrombocytosis. In PTH (group I patients) there was a sustained elevation of the platelet count lasting for several years accompanied by stable other blood values. Early AMM (group II patients) was characterized by an insidious decline of the initially elevated thrombocyte count, starting in a few patients already 4-6 months after admission. In AMM there was further an increase in hepatosplenomegaly observable together with the level of LDH and the score of the leukocyte alkaline phosphatase, and finally an evolution of a leukoerythroblastic blood picture could be noticed. Initial histopathology of the bone marrow revealed a profound proliferation of a not severely dysplastic megakaryopoiesis in group I patients (PTH) and a normal content of reticulin fibers. In early thrombocythemic AMM (group II patients) conspicuous abnormalities of megakaryocytes were accompanied by a slight to moderate increase in argyrophilic fibers and a left-shifted neutrophilic granulocyto- as well as erythropoiesis. These differences of certain histomorphological features could be substantiated by morphometric analysis. Our findings suggest that even the rigid requirements for the diagnosis of PTH as proposed by the PVSG may not be sufficiently restrictive to exclude patients with early hyperplastic stages of thrombocythemic AMM.
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PMID:Primary (essential) thrombocythemia versus initial (hyperplastic) stages of agnogenic myeloid metaplasia with thrombocytosis--a critical evaluation of clinical and histomorphological data. 247 28

Biomaterial implantation in animals is commonly used for biocompatibility studies as well as examination of long-term interaction between tissue and the test material. An in vitro cell culture model is proposed as an alternative which will save animal lives and reduce the pain and discomfort of animals used for such studies. In this study the biomaterial was matched to the cell types typical of the implant site of the particular material: porous calcium phosphate ceramic, used as dental and orthopaedic implants, with periosteal fibroblasts, osteoblasts and chondrocytes. All three cell types attached on to the ceramic and formed multicellular layers. Numbers of periosteal fibroblasts, osteoblasts and chondrocytes increased 29-, 23- and 17-fold, respectively, during the 10 wk period. Osteoblasts retained their phenotypic expression by producing only Type I collagen. Parathyroid hormone (PTH, 50 nM) suppressed the alkaline phosphatase activity of osteoblasts by over 50% and increased cAMP by more than 10-fold over control cultures.
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PMID:Growth of osteoblasts on porous calcium phosphate ceramic: an in vitro model for biocompatibility study. 254 Aug 46

The studies presented in this report describe an initial characterization of cell types derived from explants of human periodontia. Cell cultures were established from human periodontal ligament (PL4, PL7), gingival tissue (GF2), and alveolar bone (BP1) by means of explant techniques and monolayer culture. Cells were studied at passage numbers 2-4 and were characterized on the basis of morphological, biochemical, and proliferative parameters. Subconfluent cells did not have distinct morphologies useful in distinguishing them from one another. At confluence, PL4 and BP1 cells formed multilayered cultures of randomly oriented cells, while PL7 and GF2 cells grew in a monolayer of parallel cells. Biochemically, PL4 and BP1 cells exhibited characteristics consistent with an osteoblast-like phenotype. These included a significant increase in PTH-stimulated cyclic AMP and high basal levels of alkaline phosphatase activity, which were decreased on exposure to PTH and increased after stimulation by 1.25 dihydroxyvitamin D3. In contrast, PL7 and GF2 cells exhibited basal alkaline phosphatase levels that were low, and cyclic AMP levels were not modulated by PTH stimulation. Cell populations PL7 and GF2 did not proliferate in culture medium supplemented with 3% platelet-poor plasma. After the addition of platelet-derived growth factor (PDGF) to this medium, the proliferation of these cell populations was equal to that in media supplemented with 10% fetal bovine serum. In contrast, PL4 and BP1 cells did proliferate in culture medium supplemented with 3% platelet-poor plasma. The addition of PDGF to the medium resulted in only a moderate increase in the proliferation of cell populations PL4 and BP1.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Initial characterization of cells derived from human periodontia. 254 Nov 86

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


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