Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.3.1 (alkaline phosphatase)
 47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Silicon in trace amounts enhances bone formation, and the silicon-containing compound zeolite A (ZA) increases eggshell thickness in hens. In the studies reported here, treatment of nearly homogeneous strains of normal human osteoblast-like cells for 48 h with ZA at 0.1-100 micrograms/ml induced a dose-dependent increase (r = 0.35, P < 0.001) in DNA synthesis (n = 31) to 162 +/- 16% (mean +/- SEM) of control and in the proportion of cells in mitosis (n = 4) from 9.1 +/- 1.8 to 27.0 +/- 4.5% (r = 0.69, P < 0.005). ZA treatment also increased alkaline phosphatase activity (P < 0.05) and osteocalcin release (P < 0.05) but did not significantly affect collagen production per individual cell. The mitogenic action of ZA was dependent on cell seeding density over the range of 1250-40,000 cells per cm2, which is consistent with induction of an autocrine factor(s). TGF-beta is a potent mitogen for osteoblasts. ZA treatment increased the steady-state mRNA levels of transforming growth factor beta 1 (TGF-beta 1) and induced the release of the latent form of TGF-beta protein into the conditioned medium within 6 h. We conclude that ZA induces the proliferation and differentiation of cells of the osteoblast lineage.
 ...
PMID:Zeolite A increases proliferation, differentiation, and transforming growth factor beta production in normal adult human osteoblast-like cells in vitro. 133 16

The purpose of the study was to investigate the effect of skeletal growth factor/insulinlike growth factor II and other growth factors known to be present in bone matrix on the proliferation and differentiation of human bone cells. Cells were isolated by collagenase digestion from femoral heads obtained during hip replacement operations. Cells were cultured in DMEM medium with 10% calf serum. Third to fifth passage cells were plated in multiwell plates and the medium changed to low serum (0.1%) for 2 days. The medium was changed to serum-free medium prior to addition of growth factors. Cell proliferation was measured by the incorporation of [3H]thymidine into DNA and by the percentage of cells that incorporate bromodeoxyuridine. Protein synthesis was measured by the incorporation of [3H]proline into trichloroacetic acid-precipitable material. Skeletal growth factor/insulinlike growth factor II and insulinlike growth factor I stimulated cell proliferation and protein synthesis in a dose-dependent manner. Alkaline phosphatase-specific activity was not increased by these factors. Transforming growth factor beta 1 did not affect cell proliferation but stimulated protein synthesis and increased the specific activity of alkaline phosphatase. Fibroblast growth factor did not affect any of the cell parameters. These studies suggest that skeletal growth factor/insulinlike growth factor II, insulinlike growth factor I, and transforming growth factor beta 1 may play a role in the local control of the proliferation and differentiation of human osteoblasts.
 ...
PMID:Skeletal growth factor and other growth factors known to be present in bone matrix stimulate proliferation and protein synthesis in human bone cells. 215 9

The expression of transforming growth factor beta 1 (TGF-beta 1) mRNA has been determined in 16 breast carcinomas using in situ hybridization and compared with TGF-beta protein as detected by antibodies against TGF-beta 1 and TGF-beta 1 plus TGF-beta 2. Digoxigenin-labelled riboprobes were used, with alkaline phosphatase and immunogold silver detection systems. TGF-beta 1 mRNA was only detected in carcinomas in which TGF-beta 1 protein was found (9 of 16 cases) and not in those with prominent reactivity for TGF-beta 2. RNA preservation was poor in two other cases in which TGF-beta 1 protein had been detected. In general, those tumours with greater numbers of cells labelled for TGF-beta 1 mRNA had prominent reactivity for TGF-beta 1 protein. The mRNA was localized to cancer cells with no labelling of stromal cells, although in a small number of cases scanty staining for TGF-beta 1 protein had been observed in stromal cells. The incidence of detection of TGF-beta 1 mRNA is lower than the published data from Northern analysis studies of breast carcinomas, suggesting that only higher levels of TGF-beta 1 mRNA expression are being detected by in situ hybridization. However, this approach has provided useful information about the cellular sites of expression of TGF-beta 1 in breast carcinomas.
 ...
PMID:Determination of transforming growth factor beta 1 mRNA expression in breast carcinomas by in situ hybridization. 749 Jun 77

Human bone marrow contains a distinct cell population that expresses bone proteins and responds to transforming growth factor beta 1 (TGF-beta), but not to hematopoietic growth factors (Long, M. W., J. L. Williams, and K. G. Mann. 1990. J. Clin. Invest. 86:1387-1395). We now report the isolation, characterization, and growth factor responsiveness of these precursors to human osteoblasts and the identification of a human osteoprogenitor cell. Immunological separation of human bone marrow nonadherent low-density (NALD) cells results in a marked enrichment of cells that express osteocalcin, osteonectin, and bone alkaline phosphatase. Flow cytometric analyses show that distinct cell subpopulations exist among these isolated cells. The majority of the bone antigen-positive cells are approximately the size of a lymphocyte, whereas other, less frequent antibody-separated subpopulations consist of osteoblast-like cells and osteoprogenitor cells. In serum-free cultures, TGF-beta stimulates the small, antigen-positive cells to become osteoblast-like, as these cells both increase in size, and express increased levels of osteocalcin and alkaline phosphatase. Antibody-separated cells also contain a separate population of clonal progenitor cells that form colonies of osteoblast-like cells when cultured in serum-free, semi-solid media. Two types of human osteoprogenitor cells are observed: a colony-forming cell (CFC) that generates several hundred bone antigen-positive cells, and a more mature cluster-forming cell that has a lesser proliferative potential and thus generates clusters of 20-50 antigen-positive cells. Osteopoietic colony-forming cells and cluster-forming cells have an obligate but differential requirement for osteogenic growth factors. The CFCs respond to TGF-beta, basic fibroblast growth factor (bFGF), bone morphogenic protein-2 (BMP-2), and 1, 25-dihydroxy vitamin D3 (1,25-OH D3). In contrast to the colony-forming cells, cluster-forming cells are regulated predominantly by 1,25-OH D3 and TGF-beta, but fail to respond to bFGF. We conclude that human bone marrow contains a nonhematogenous, heterogeneous population of bone precursor cells among which exists a population of proliferating osteoprogenitor cells. Further characterization of these bone precursor cell populations should yield important information on their role in osteogenesis in both health and disease.
 ...
PMID:Regulation of human bone marrow-derived osteoprogenitor cells by osteogenic growth factors. 786 Jul 71

A five-point linkage map has been established between the loci encoding liver/bone/kidney alkaline phosphatase (ALPL), enolase 1-alpha (ENO1), glucose-phosphate isomerase (GPI), phosphogluconate dehydrogenase (PGD), and transforming growth factor beta 1 (TGFB1) in swine. Linkage analysis was performed using the Meishan x Yorkshire three-generation reference pedigree at the University of Illinois (n = 91). Previously ENO1, GPI, PGD, and TGFB1 were mapped to porcine chromosome 6q by in situ hybridization but the linkage relations of TGFB1 and ENO1 with other loci in this group were not investigated. Based on mapping data from human chromosomes 1 and 19 and mouse chromosomes 4 and 7, it was postulated that ALPL should reside among or near these loci. Restriction fragment length polymorphisms were identified for ALPL, ENO1, and TGFB1. GPI (EC 5.3.1.9) and PGD (EC 1.1.1.44) phenotypes were determined by agarose gel electrophoresis of isozymes. Marker data were analyzed using the MLINK (two locus) and ILINK (multilocus) programs from LINKAGE (version 5.10). The most likely locus order between GPI-TGFB1-(PGD-ENO1)-ALPL with recombination rates of 0.049, 0.044, 0.000, and 0.156, respectively, could not be significantly determined. The maximum five-point lod score was the same to four decimal places irrespective of the order of ENO1 and PGD. This indicates that ENO1 and PGD are very closely linked and that ALPL is located telomeric to the established linkage group on pig chromosome 6.
 ...
PMID:Linkage relationships between ALPL, ENO1, GPI, PGD, and TGFB1 on porcine chromosome 6. 810 72

Selected G1 events associated with butyrate-induced differentiation were examined in HT-29 colon adenocarcinoma cells. [3H]Thymidine incorporation by HT-29 cells was decreased to 40% of control levels by treatment with 5 mM butyrate for 24 h, and cell numbers decreased to 21% of control levels after 48 h of treatment. Cells released from butyrate arrest entered S phase approximately 24 h after release, and serum-deprived HT-29 cells escaped growth inhibition if butyrate was added 8 h or more after serum restimulation. Northern analysis of RNA isolated from rapidly growing HT-29 cells showed a marked induction of alkaline phosphatase mRNA expression within 12 h of treatment with 5 mM butyrate. The appearance of alkaline phosphatase mRNA was temporally associated with a 5-fold increase in expression of transforming growth factor beta 1 (TGF-beta 1) mRNA. Expression of the nuclear protooncogene c-myc began to decrease 30 min after treatment with butyrate and was decreased 4.5-fold 4 h after treatment; however, expression of other immediate-early genes (nup/475 and zif/268) was not significantly affected. Histochemical staining of HT-29 monolayers showed that no cells were positive for alkaline phosphatase protein prior to treatment, and 90% were positive 48 h after treatment. TGF-beta 1 and TGF-beta 2 had no effect on HT-29 cell growth. TGF-beta 1 did not induce alkaline phosphatase mRNA or histochemical positivity. These data indicate that butyrate arrests HT-29 cell growth early in G1.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Butyrate rapidly induces growth inhibition and differentiation in HT-29 cells. 837 33

Following injury to bone marrow there is a phase of osteogenesis in which bone trabeculae replace the initial blood clot and fill the marrow cavity. The newly formed bone is subsequently fully resorbed by osteoclasts and normal bone marrow is restored. In this study we correlated the morphologic events with the pattern of gene expression that defines this sequence. Following marrow ablation, the trabecular bone volume in the affected section of the marrow cavity increased from control to 27% at day 6, declined to 18% at day 8, and eventually returned to control levels at day 14. Osteoblast number increased up to day 6 and declined substantially by day 8, but the number of osteoclasts peaked between days 8 and 10. Histologic analysis of alkaline phosphatase (AP) and tartrate-resistant acid phosphatase (TRAP) activity correlated with the observed cellular changes. Northern blot analysis of the levels of AP, osteocalcin (OC), and osteopontin (OP) mRNA shows a specific pattern of regulated gene expression, with AP mRNA maximal at day 6, OC mRNA very low until days 6-8, and OP mRNA expressed at very high levels throughout. In addition, procollagen alpha 1(I) and alpha 1(III) mRNAs show a regulated pattern of expression, with procollagen alpha 1(I) maximally expressed between days 4 and 10 and procollagen alpha 1(III) expressed at lower levels between days 4 and 6. The mRNA encoding insulin-like growth factor I (IGF-I) was found to be highly expressed between days 5 and 12; however, transforming growth factor beta 1 (TGF-beta 1) and TGF-beta 3 mRNA were only weakly expressed between days 4 and 10. These data demonstrate a temporal pattern of gene expression consistent with the observed morphologic profile, identify changes in growth factor mRNA that may be related to this repair process, and suggest that this is a suitable model for studying in vivo a synchronized sequence of bone formation and resorption at a well-defined anatomic site.
 ...
PMID:Pattern of gene expression following rat tibial marrow ablation. 845 91

We tested the hypothesis that there is direct end-organ resistance to growth hormone (GH) and IGF-I in chronic renal failure (CRF) independent of circulating inhibitors. Male Sprague-Dawley rats underwent 5/6 nephrectomy and were pair-fed with weight matched (100 g) sham operated controls for two weeks. Rats with CRF had significantly higher serum creatinine and blood urea nitrogen (P < 0.01 in both cases) and gained significantly less weight and length (P < 0.01 in both cases) compared with controls. Epiphyseal chondrocytes were grown in 10% fetal calf serum (FCS). Both CRF cells and control cells maintained chondrogenic phenotypes, and showed immunohistochemical staining with antibodies to collagen II and proteoglycan (aggrecan). Distribution of the cell subpopulations according to cell size (by flow cytometry) and alkaline phosphatase activity of CRF and control chondrocyte cultures were not different. Growth responses of CRF chondrocytes were reduced (P < 0.01) compared with control chondrocytes when grown in 10% FCS and 10% normal rat serum. Under serum free conditions, growth responses of CRF chondrocytes were reduced to GH and IGF-I at concentrations of 10, 30 and 100 ng/ml, and to insulin at 100, 300 and 1,000 ng/ml compared with controls cells (P < 0.01). To show that this resistance is specific for the GH/IGF system, growth responses to fibroblast growth factor and transforming growth factor beta 1 were studied and showed no difference between CRF and control cells. Thus, the present study provides direct evidence of specific end-organ resistance to GH, IGF-I in CRF chondrocytes in the absence of circulating factors.
 ...
PMID:End-organ resistance to growth hormone and IGF-I in epiphyseal chondrocytes of rats with chronic renal failure. 884 Feb 66

A human osteoblastic cell line (SV-HFO) established in our laboratory expresses osteoblastic markers, including mineralization in vitro, in response to differentiation-inducing agents such as dexamethasone. In this study, we examined the effects of transforming growth factor beta 1 (TGF-beta 1) on the mineralization of SV-HFO cells and show that TGF-beta 1 inhibited the mineralization of the cells via down regulation of tetranectin and alkaline phosphatase without influencing other osteoblastic markers. To examine precisely the effects of TGF-beta 1 on the process of mineralization, we tentatively divided the whole process of mineralization into four phases: induced ALP activity (days 0-5), maximal ALP activity (days 5-10), early mineralization (days 10-15), and progressive mineralization (days 15-20). These inhibitory effects of TGF-beta 1 on the expression of tetranectin and alkaline phosphatase, like that on mineralization, were observed only when TGF-beta 1 was applied in the early phase of the process of mineralization. On the other hand, the other osteoblastic markers were not influenced by treatment with TGF-beta 1. These results suggest that TGF-beta 1 may inhibit mineralization of osteoblasts by the downregulation of tetranectin and alkaline phosphatase expression in the early phase. Thus, TGF-beta 1 has phase-dependent effects on a human osteoblastic cell line during the process of mineralization.
 ...
PMID:Phase-Dependent effects of transforming growth factor beta 1 on osteoblastic markers of human osteoblastic cell line sV-HFO during mineralization. 889 42

A purified bone-inducing protein complex (BIC), isolated from bovine bone and causing de novo bone formation in vivo, induces defined effects on rat mesenchymal cells in vitro. Spindle-like mesenchymal cells growing in monolayers change to polygonal cells, forming a multilayered growth pattern. The mesenchymal cells acquire alkaline phosphatase activity. Upon culture with BIC, the typical collagen Type III deposition of these mesenchymal cells is remarkably reduced whereas the collagen Type I expression remains unaffected. All these in vitro effects are consistent with the strong bone-forming capacity of BIC in vivo. A combination of two cytokines, transforming growth factor beta 1 (TGF beta 1) and epidermal growth factor (EGF), shows a similar activity to BIC. Neutralizing anti-TGF beta antibodies interfere with all in vitro effects of BIC. The neutralization of BIC and the inductive capacity of the combination of TGF beta 1 plus EGF point to the substantial role of TGF beta or TGF beta-like molecules in BIC; whether the active polypeptides are identical to TGF beta or somewhat structurally homologous to TGF beta remains to be elucidated.
 ...
PMID:Effects of a new bone-inducing biomaterial on mesenchymal cells in vitro. 1007 74


1 2 3 Next >>