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)

Daily subcutaneous injections of rat derived growth hormone to immature, hypophysectomized rats stimulated significant increases in body weight gain, serum osteocalcin, skeletal alkaline phosphatase and incorporation of radioactive thymidine and proline into the compact bone of femurs and tibiae. Equimolar doses of insulin-like growth factor-II did not produce similar biological effects. The data support the contention that growth hormone at equimolar concentration is a stronger osteogenic agent than is insulin-like growth factor-II in vivo.
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PMID:Growth hormone stimulates cortical bone formation in immature hypophysectomized rats. 157 75

In order to determine which clinical, anthropometric, dietary, and biochemical variables are independent predictors of total and regional bone mineral density (BMD) in normal postmenopausal women, a cross-sectional study of 140 normal postmenopausal women has been carried out. Subjects were white, aged 45-71 yr (mean 58 yr), and had no history of disorders or medication use likely to influence bone or calcium metabolism. Multiple regression analysis was used to derive models for total and regional BMD in terms of the other variables measured. The analysis indicated that total body BMD was positively related to fat mass (P less than 0.0001), serum estrone (P = 0.0095) and age at menopause (P = 0.0165), and negatively related to age (P less than 0.0001), 24-h urine calcium (P = 0.0002), sex hormone-binding globulin (P = 0.0003), and serum alkaline phosphatase activity (P = 0.0029) (R2 = 0.61). Similar relationships were found in the subregions of the total body scans and in the lumbar spine and proximal femur, with insulin-like growth factor-1, parity, and age at menarche also being related to BMD at at least two of these sites. Lean body mass was not an independent correlate of BMD at any site once fat mass was taken into account. Muscle strength, physical activity, alcohol intake, and dietary intakes of calcium, sodium and protein did not emerge as significant predictors of BMD in this homogeneous group of postmenopausal women. We conclude that total body fat is the most significant predictor of BMD throughout the skeleton and this relationship is not explicable in terms of either estrone production in fat tissue or the dependence of skeletal load-bearing on fat mass. The mechanism underlying this relationship is an important question to be addressed in bone biology.
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PMID:Determinants of total body and regional bone mineral density in normal postmenopausal women--a key role for fat mass. 161 30

The insulin-like growth factor-binding protein IGF-BP1 is a major secretory protein of human endometrial stromal cells decidualized in culture. Anion exchange chromatography and nondenaturing gel electrophoresis showed IGF-BP1 to exist in five electrophoretically and chromatographically distinct isoforms. IGF-BP1 variants migrated as a quintet on nondenaturing polyacrylamide gels and as a single band (28 kDa) on sodium dodecyl sulfate-polyacrylamide gels. Alkaline phosphatase treatment reduced the IGF-BP1 variants to a single band. Cells incubated with [32P]orthophosphate for 12 h secreted four 32P-labeled IGF-BP1 phosphovariants, and their migration coincided with those bands that were eliminated by alkaline phosphatase treatment. In cells treated with medroxyprogesterone acetate and relaxin, the concentration of phosphorylated IGF-BP1 was increased dramatically as compared with controls. All the phosphovariants were confirmed to be IGF-BP1 by their ability to be supershifted on nondenaturing polyacrylamide gels after binding a monoclonal antibody to IGF-BP1. Thin layer electrophoresis of IGF-BP1 acid hydrolysates showed IGF-BP1 to be phosphorylated exclusively on serine. Non-phosphorylated IGF-BP1 was phosphorylated by the catalytic subunit of the cAMP-dependent protein kinase and casein kinase II in vitro. This suggests that IGF-BP1 may be a substrate of multiple protein kinases in vivo.
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PMID:Insulin-like growth factor-binding protein-1 is phosphorylated by cultured human endometrial stromal cells and multiple protein kinases in vitro. 165 36

Twice or three times daily intranasal administration of the hexapeptide hexarelin for 7 days to children with short stature and normal growth hormone (GH) secretion evoked a significant rise in serum levels of insulin-like growth factor-1 (IGF-1) and alkaline phosphatase. There was also a significant, within normal limits, rise of thyroid stimulating hormone (TSH) without evidence of thyroxine suppression.
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PMID:Short term effect of intranasal administration of hexarelin--a synthetic growth hormone-releasing peptide. Preliminary communication. 758 96

The effects of platelet-derived growth factor (PDGF) on DNA synthesis and mRNA expression of osteoblast markers in marrow stromal cells derived from adult (6 months) and old (24 months) rats were examined. Treatment of stromal cells from adult rats with dexamethasone induced the appearance of osteoblast-like cells. PDGF partially also inhibited the differentiation of stromal cells induced by dexamethasone. In cultures of serum-starved stromal cells, PDGF stimulated [3H]-thymidine incorporation into DNA in a dose-dependent manner with a maximum stimulation of 15-fold at 500 ng/ml. By comparison, insulin-like growth factor (IGF-I) has a small effect on [3H]-thymidine incorporation. The effect of PDGF and IGF-I on DNA synthesis was additive. Treatment of the confluent stromal cells from adult rats with PDGF increased the mRNA level of osteopontin fourfold without any significant effect on alkaline phosphatase and type I collagen mRNAs. In contrast, dexamethasone stimulated the mRNA expression of alkaline phosphatase, type I collagen, and osteopontin 2.1-, 2.3-, and 14-fold, respectively. Addition of PDGF to dexamethasone-treated cells failed to induce any further increase in osteopontin expression whereas the expression of alkaline phosphatase and type I collagen was partially reduced. The expression of osteocalcin mRNA was negligible in stromal cells but stimulated several fold by dexamethasone and 1,25(OH)2D3. PDGF inhibited drastically the elevation of osteocalcin mRNA. In contrast, IGF-I stimulated type I collagen expression 100% without any appreciable effect on the expression of osteopontin and alkaline phosphatase. The stimulatory effect of PDGF on osteopontin expression was augmented by IGF-I. Furthermore, PDGF attenuated the stimulatory effect of IGF-I on type I collagen expression. The responses of cultured cells from old rats to growth factors were also examined. PDGF or PDGF plus IGF-I increased [3H]-thymidine incorporation in stromal cells from old rats but to a lesser extent. However, PDGF was equally effective in stimulating osteopontin expression in cells from both adult and old rats. We concluded that PDGF is a potent mitogen but that the response of stromal cells from old rats is impaired. In addition, PDGF stimulates osteopontin expression in stromal cells and this effect is not age dependent.
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PMID:Effect of platelet-derived growth factor on DNA synthesis and gene expression in bone marrow stromal cells derived from adult and old rats. 762 82

In the present study, we have sought to determine whether a given signal transduction pathway can have diverse effects on subpopulations of cells of a lineage depending upon the stage of differentiation. To test this hypothesis, we selected the cyclic adenosine monophosphate (cAMP) signal transduction pathway because of its recognized importance in mediating the actions of many hormones, e.g., parathyroid hormone which acts on the bone-forming cells, the osteoblasts. Subpopulations of human osteosarcoma SaOS-2 cells with low (LSaOS) and high (HSaOS) alkaline phosphatase (ALP) content were chosen as model systems for preosteoblasts (pre-OB) and osteoblasts (OB), respectively. Dibutyryl cyclic AMP (DBcAMP) treatment of serum free cultures produced a differential effect on the proliferation of LSaOS cells (40 +/- 5% of control at 1 mM DBcAMP, P < 0.001) compared with HSaOS cells (no statistically significant effect). The finding supports the hypothesis. Next, we sought evidence for mediation, at least in part, by the insulin-like growth factor (IGF)-II regulatory system. We report that the basal expression of IGF-II, IGF binding protein (IGFBP)-3, and IGFBP-4 was higher in LSaOS cells than in HSaOS cells with the opposite true for type I IGF receptor. DBcAMP treatment of LSaOS cells decreased IGF-II and IGFBP-3 but increased IGFBP-4 and type I IGF receptor; no effect was observed for the type II IGF receptors. DBcAMP treatment of HSaOS cells had no detectable effect on IGF-II; IGFBP-3, or type I and type II IGF receptor expression; only IGFBP-4 expression increased with DBcAMP. These observations suggest that the differential regulation of cell proliferation by the cAMP signal transduction pathway may be mediated, at least in part, by the IGF-II regulatory system.
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PMID:Dibutyryl cyclic adenosine monophosphate differentially regulates cell proliferation in low and high alkaline phosphatase SaOS-2 human osteosarcoma cells: evidence for mediation by the insulin-like growth factor-II system. 768 70

Different fractions of insulin-like growth factor-binding protein-1 (IGFBP-1) from anion exchange chromatography represent differently phosphorylated forms as demonstrated by protein kinase and alkaline phosphatase treatments. The major fraction is non-phosphorylated. Three minor fractions are more phosphorylated and, in native polyacrylamide gel electrophoresis (PAGE), they migrate faster than the major fractions. We studied the changes in phosphorylation of decidual and amniotic fluid IGFBP-1 during pregnancy. Both in decidua and in amniotic fluid the degree of phosphorylation increased from early to late pregnancy, as indicated by faster mobility of IGFBP-1 in native PAGE and increased relative amount of the phosphorylated forms in anion exchange chromatography. The more phosphorylated forms had higher IGF-binding affinity than the less phosphorylated forms. As the degree of phosphorylation of IGFBP-1 is highest in full term decidua it is likely that the inhibitory role of IGFBP-1 is accentuated in the end of pregnancy.
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PMID:Phosphorylation of insulin-like growth factor-binding protein-1 increases in human amniotic fluid and decidua from early to late pregnancy. 769 47

Corticosteroid therapy causes osteopenia and growth retardation in children; such changes are associated with diminished rates of bone formation and turnover. Since growth hormone activates bone remodeling, the biochemical and skeletal responses to rhGH were evaluated in four pediatric patients, aged 12.8 +/- 3 years, with long-term corticosteroid use (5 +/- 2 years). Recombinant human growth hormone (rhGH), 0.125 mg/kg, was given 3 times/week by subcutaneous injection for 12 months. Iliac crest bone biopsies were obtained after double tetracycline labeling before and at the end of rhGH therapy; serum levels of calcium, phosphorus, alkaline phosphatase, parathyroid hormone (intact), 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D3, osteocalcin (BGP), and insulin-like growth factor-1 (IGF-1) were measured every 3 months during the treatment period. The average dose of prednisone was 0.24 +/- 0.05 mg/kg/day initially, and this did not change during the study. Serum calcium, phosphorus, alkaline phosphatase, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D3, and BGP were unchanged during the rhGH therapy, but the serum IGF-1 level increased by 71%, p < 0.01. Eroded bone perimeter and cancellous bone area did not change significantly during rhGH therapy. Bone formation rates rose from 423 +/- 475 to 781 +/- 407 microns2/mm2/day, p < 0.05, and the length of double tetracycline-labeled bone perimeter increased by 85%, p < 0.05. The bone formation rate in the growth hormone group exceeded the values of an age-matched reference group (14.3 +/- 3 years), 780 +/- 407 microns2/mm2/day versus 411 +/- 479 microns2/mm2/day, p < 0.05.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Skeletal response to recombinant human growth hormone (rhGH) in children treated with long-term corticosteroids. 774 27

At Day 17 of in ovo development, chondrocyte hypertrophy including synthesis of collagen X takes place in a limited region within the cranial part of chick embryo sternum. Here we analyze in suspension culture the differences in response to single growth factors of chondrocytes derived from the cranial part versus cells derived from the caudal part. Cells from either part were cultured separately without serum in the presence of insulin-like growth factor-1, transforming growth factor beta 2, basic fibroblast growth factor, or thyroid hormones. In culture, chondrocytes derived from the cranial part of sterna from 14- to 18-day-old chicken embryos become hypertrophic and initiated the synthesis of collagen X and alkaline phosphatase. These processes were enhanced by anabolic diffusible signals, such as those contained in fetal bovine serum, insulin-like growth factor-1, or thyroxine. Cells derived from the caudal part lack this capacity and, instead, prevented hypertrophy of cranial cells in cocultures, presumably by secreting diffusible signals. As candidate molecules, we have identified transforming growth factor beta 2 and basic fibroblast growth factor, which both were released by chondrocytes. Synergistic action of transforming growth factor beta 2 and basic fibroblast growth factor was required to suppress insulin-like growth factor-1-stimulated maturation of cranial chondrocytes in culture.
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PMID:Terminal differentiation of chondrocytes in culture is a spontaneous process and is arrested by transforming growth factor-beta 2 and basic fibroblast growth factor in synergy. 781 20

The present study was performed to examine whether calcitonin directly acted on mouse osteoblastic MC3T3-E1 cells to stimulate the mRNA expression of insulin-like growth factor-1 (IGF-1) and c-fos, followed by an increase in their proliferation and differentiation. Eel calcitonin increased [3H]thymidine incorporation and alkaline phosphatase activity as well as the mRNA expression of type 1 collagen and osteocalcin which were characteristic of osteoblasts. Eel calcitonin (10(-8)M) induced c-fos mRNA transiently after its addition, followed by gene expression of IGF-1, an important autocrine/paracrine growth factor in the regulation of osteoblastic proliferation. We first demonstrated that calcitonin directly acted on osteoblasts to stimulate transcription of c-fos and IGF-1 genes as well as functional phenotypes including type 1 collagen and osteocalcin.
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PMID:Calcitonin directly acts on mouse osteoblastic MC3T3-E1 cells to stimulate mRNA expression of c-fos, insulin-like growth factor-1 and osteoblastic phenotypes (type 1 collagen and osteocalcin). 813 34


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