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 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

Transforming growth factor beta (TGF-beta), a potent regulator of bone formation, has bifunctional effects on osteoblast replication and biochemical activity that appear differentiation dependent. We now show that cell surface binding sites for TGF-beta vary markedly among fibroblasts, bone-derived cells, and highly differentiated osteosarcoma cultures from fetal rats. Expression of betaglycan and type II receptors decline relative to type I receptor expression in parallel with an increase in osteoblast-like activity, predicting that the ratio among various TGF-beta binding sites could influence how its signals are perceived. Bone morphogenetic protein 2 (BMP-2), which induces osteoblast function, does not alter TGF-beta binding or biochemical activity in fibroblasts and has only small effects in less differentiated bone cells. In contrast, BMP-2 rapidly reduces TGF-beta binding to betaglycan and type II receptors in osteoblast-enriched primary cell cultures and increases its relative binding to type I receptors in these cells and in ROS 17/2.8 cultures. Pretreatment with BMP-2 diminishes TGF-beta-induced DNA synthesis in osteoblast-enriched cultures but synergistically enhances its stimulatory effects on either collagen synthesis or alkaline phosphatase activity, depending on the present state of bone cell differentiation. Therefore, BMP-2 shifts the TGF-beta binding profile on bone cells in ways that are consistent with progressive expression of osteoblast phenotype, and these changes distinguish the biochemical effects mediated by each receptor. Our observations indicate specific stepwise actions by TGF-beta family members during osteoblast differentiation, developing in part from changes imprinted by BMP-2 on TGF-beta receptor stoichiometry.
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PMID:Independent changes in type I and type II receptors for transforming growth factor beta induced by bone morphogenetic protein 2 parallel expression of the osteoblast phenotype. 776 Aug 23

The effects of recombinant human bone morphogenetic protein 2 (rhBMP-2) on osteochondrogenesis were examined in high-density cultures of periosteum-derived cells, which have the potential to differentiate into bone and hypertrophic cartilage in vitro. Proliferation of these cells was inhibited by treatment with rhBMP-2. The time course for alkaline phosphatase (ALP) expression was shortened and the mineralization of the culture was increased by supplementation with rhBMP-2. These stimulatory effects of rhBMP-2 were observed at doses of 10-100 ng/m. Bone Gla protein (BGP) was immunocytochemically detectable earlier in the culture treated with rhBMP-2, and the BGP-positive layer of the rhBMP-2-treated cultures was thicker than that of the control cultures. On the other hand, there was no difference in uronic acid content or the time course of alpha 1(II) collagen mRNA expression between the rhBMP-2-treated and the control cultures. These results indicate that rhBMP-2 shortens the time course of osteogenesis and increases the amount of bone formation, whereas chondrogenesis remains unaffected.
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PMID:Bone morphogenetic protein 2 stimulates osteogenesis but does not affect chondrogenesis in osteochondrogenic differentiation of periosteum-derived cells. 797 2

Transforming growth factor beta (TGF-beta) is one of the most abundant of the known growth regulatory factors stored within the bone matrix. When bone is resorbed, TGF-beta is released in an active form and is a powerful bone growth stimulant. When injected into the subcutaneous tissue over the calvarial surface of rodents, it rapidly causes proliferation of the periosteal layer and accumulation of new woven bone. In this report, we describe the effects of TGF-beta 1 on first subcultures of fetal rat osteoblasts obtained from calvarial bones and cultured from confluence with ascorbic acid and beta-glycerophosphate. Under these conditions, nodules with characteristics of normal bone appear by day 8. Similar to experiments described by Antosz et al., TGF-beta added to confluent cultures inhibited the formation of bone nodules. Both the number and total area of the nodules were quantitated and shown to be completely inhibited by 2 ng/ml of TGF-beta 1. TGF-beta also impaired the expression of genes associated with bone formation, including type I collagen, alkaline phosphatase, osteopontin, and osteocalcin. TGF-beta also inhibited the expression of mRNA for the bone morphogenetic protein 2 (BMP-2). These results, showing suppression of markers representative of osteoblast differentiation, suggest that the effects of TGF-beta to stimulate bone formation in vivo are not likely a result of effects on differentiated mineralizing osteoblasts but, as suggested by previous studies, more likely are caused by effects on osteoblast precursors. These results also suggest that endogenous BMP-2 expression in fetal rat calvaria cells is important for bone cell differentiation.
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PMID:Effects of transforming growth factor beta on bone nodule formation and expression of bone morphogenetic protein 2, osteocalcin, osteopontin, alkaline phosphatase, and type I collagen mRNA in long-term cultures of fetal rat calvarial osteoblasts. 807 61

In this study, we attempted to purify the dimeric BMP-2 from extracts of Xenopus embryos in order to show the presence of BMP-2 activity in the embryos. Immunoreactive BMP-2 protein was found to be a homodimer of an 18 kDa BMP-2 polypeptide linked through disulfide bridge(s). Biological activities of the partially purified dimeric BMP-2 were examined in vitro. The Xenopus BMP-2 induced alkaline phosphatase in a dose-dependent manner in cultured osteoblastic cells, MC3T3-E1. The inducing activity was synergistically enhanced by the presence of retinoic acid. The results showed that the dimeric form of Xenopus BMP-2 has an indistinguishable biological activity from that of mammalian BMP-2.
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PMID:Biologically active BMP-2 in early Xenopus laevis embryos. 811 84

Vasculotropin/vascular endothelial growth factor (VAS/VEGF) is an angiogenic growth factor whose biological activity seems to be restricted in vitro to vascular endothelial cells. We describe here that fetal bovine osteoblasts (OB) bind VAS/VEGF but do not proliferate upon its addition. However VAS/VEGF induces migration, PTH-dependent cAMP accumulation and alkaline phosphatase increase when added to OB. The maximal effects reach levels comparable to that obtained with bone morphogenetic protein 2 (BMP-2), although the VAS/VEGF concentrations required are at least 100 fold lower. Our results suggest that VAS/VEGF could be an important regulator of osteoblastic differentiation.
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PMID:Vasculotropin/vascular endothelial growth factor induces differentiation in cultured osteoblasts. 812 39

The expression of developmental stage-specific genes during pulp cell differentiation into preodontoblasts was examined in bovine adult pulp cell culture. When proliferation was down-regulated after 14 days of primary culture, expression of fibronectin and type I and type III collagen mRNAs was increased. Expression of alkaline phosphatase was gradually increased, and mRNA for osteocalcin, a marker of preodontoblast, appeared just before the onset of mineralization. Contrarily, in expanded culture, the expression of mRNA for the extracellular matrix proteins was gradually increased from the beginning of culture up to Day 28. Similarly, mRNA levels of alkaline phosphatase and osteocalcin were also increased gradually. Expression of TGF-beta 1 mRNA disappeared on Day 21 in the primary culture when expression of alkaline phosphatase mRNA was increased. BMP-4 mRNA was expressed on Day 14 when the expression of the extracellular matrix proteins was increased. BMP-2 mRNA was expressed on Day 28 when osteocalcin appeared. Recombinant TGF-beta 1 inhibited alkaline phosphatase activity, while BMP-2 and BMP-4 stimulated it. BMP-4 increased expression of alpha 1(I) collagen mRNA, and BMP-2 increased osteocalcin synthesis. These results demonstrate the regulatory role of these TGF-beta superfamily members on the gene expression of extracellular matrix proteins and the differentiation of pulp cells into preodontoblasts.
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PMID:Regulatory role of transforming growth factor-beta, bone morphogenetic protein-2, and protein-4 on gene expression of extracellular matrix proteins and differentiation of dental pulp cells. 812 85

The steady-state mRNA levels of different osteogenic markers and their modulation by 17 beta-estradiol in the murine osteogenic cell line MN7 during proliferation and differentiation in vitro were examined. mRNA of collagen type I, osteopontin, bone morphogenetic protein 2, plasminogen activator inhibitor 1, alkaline phosphatase, and osteocalcin were isolated from MN7 cultures grown for 7, 11, 14, and 17 days. Northern blot analysis revealed steady-state transcript levels depending on MN7 cell density. The order of appearance of Col I, OP, ALP, and OC resembled the pattern of gene expression observed during osteoblast maturation in vitro. Furthermore, PAI-1 steady-state transcript levels peaked during subconfluence (day 11) but BMP-2 RNA levels reached their maximum after the culture had become confluent. 17 beta-Estradiol showed a dose-dependent stimulation of the different osteoblast-related transcripts present in a subconfluent MN7 culture at the time of analysis. Furthermore, the effects of 17 beta-estradiol (17 beta E2) at different time points of MN7 growth varied according to cell density. 17 beta E2 added to subconfluent MN7 cultures modulated the transcript level in a negative way, but RNA levels of the investigated osteogenic markers in confluent cultures were stimulated with 100 nM 17 beta-estradiol. No effect of 17 beta-estradiol on proliferation was detected. The present studies have revealed differential osteoblast gene expression related to MN7 cell proliferation and differentiation in vitro and emphasize the importance of 17 beta E2 in the regulation of growth of this preosteoblastic cell line in vitro.
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PMID:Characterization of the stromal osteogenic cell line MN7: mRNA steady-state level of selected osteogenic markers depends on cell density and is influenced by 17 beta-estradiol. 814 Sep 31

The cDNAs encoding the human bone morphogenetic proteins BMP-2 and BMP-4 in an eukaryotic expression vector were permanently transferred into the murine mesenchymal progenitor cell line C3H10T1/2. Originally, these cells are known to differentiate into myotubes, adipocytes, and chondrocytes upon the addition of azacytidine. Permanent transfection of genes encoding human BMP-2 and BMP-4 induces differentiation into the osteogenic lineage. The osteogenic differentiation potential of C3H10T1/2 cells is substantiated by histochemical and genetic analyses of marker genes typical or specific for osteogenesis, including the parathyroid hormone receptor, alkaline phosphatase, osteopontin, osteonectin, and osteocalcin. In addition to osteoblast formation, development into adipocytes and chondrocytes is also observed, suggesting that BMP-2 and BMP-4 induce differentiation into three mesenchymal lineages.
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PMID:Expression of human bone morphogenetic proteins-2 or -4 in murine mesenchymal progenitor C3H10T1/2 cells induces differentiation into distinct mesenchymal cell lineages. 827 20

Both decapentaplegic (dpp) protein and 60A protein have been implicated in pattern formation during Drosophila melanogaster embryogenesis. Within the C-terminal domain, dpp and 60A are similar to human bone morphogenetic protein 2 (75% identity) and human osteogenic protein 1 (70% identity), respectively. Both recombinant human bone morphogenetic protein 2 and recombinant human osteogenic protein 1 have been shown to induce bone formation in vivo and to restore large diaphyseal segmental defects in various animal models. We examined whether the Drosophila proteins, dpp and 60A, have the capacity to induce bone formation in mammals by using the rat subcutaneous bone induction model. Highly purified recombinant dpp and 60A induced the formation of cartilage, bone, and bone marrow in mammals, as determined by histological observations and by measurements of the specific activity of alkaline phosphatase and calcium content of the implants, thereby demonstrating that related proteins from phylogenetically distant species are capable of inducing bone formation in mammals when placed in sites where progenitor cells are available.
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PMID:Drosophila transforming growth factor beta superfamily proteins induce endochondral bone formation in mammals. 832 74


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