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)

We investigated the effects of insulin-like growth factor I/somatomedin C (IGF-I/SM-C), and the interaction of IGF-I and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) on mouse clonal osteoblasts, MC3T3-E1. IGF-I stimulated [3H]thymidine incorporation into the DNA of the cells at concentrations of 1.3-130 X 10(-9) M. The alkaline phosphatase (ALP) activity in cultures was also raised by the hormone at the same concentrations. The optimal dose of IGF-I was 13 X 10(-9) M. Co-addition of IGF-I (1.3-130 X 10(-9) M) and 1,25(OH)2D3 (10(-11) to 10(-10) M) to the culture of MC3T3-E1 cells caused a synergistic increase in ALP activity. 25(OH)D3 and 24,25(OH)2D3 showed a similar effect with IGF-I at 1000-2000 times higher concentrations than 1,25(OH)2D3. [3H]Proline incorporation into collagenase digestible protein (CDP) in media was stimulated dose-dependently by IGF-I up to 2.2-fold over the control levels at 130 X 10(-9) M. Addition of 1,25(OH)2D3 (5 X 10(-11) M) and IGF-I further elevated the proline incorporation into CDP. However, the increment in CDP synthesis, induced by the two hormones was less than the increment in ALP activity. Thus, we conclude (1) that IGF-I stimulates both cell replication and differentiated functions in cultured murine osteoblasts and (2) that IGF-I and 1,25(OH)2D3 have the synergistic effect on ALP activity and the additive effect on collagen synthesis in MC3T3-E1 cells.
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PMID:Cooperation of synthetic insulin-like growth factor I/somatomedin C and 1,25-dihydroxyvitamin D3 on regulation of function in clonal osteoblastic cells. 272 Feb

In cloned osteoblast-like cells, MC3T3-E1, 12-O-tetradecanoylphorbol-13-acetate (TPA), a protein kinase C activating phorbol ester, and 1-oleoyl-2-acetylglycerol (OAG), a specific activator for protein kinase C, stimulated DNA synthesis in a dose-dependent manner. Both TPA and OAG acted synergistically with insulin-like growth factor I to stimulate DNA synthesis. TPA as well as OAG suppressed the increase in alkaline phosphatase activity of MC3T3-E1 cells induced by parathyroid hormone. These results suggest that protein kinase C is involved in the process which directs osteoblast-like cells toward proliferation.
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PMID:Possible involvement of protein kinase C in proliferation and differentiation of osteoblast-like cells. 291 45

We recently proposed a hypothesis for the molecular mechanism of the osteogenic action of fluoride in which it stimulates osteoblast proliferation via the inhibition of an osteoblastic acid phosphatase-like phosphotyrosyl protein phosphatase activity. To test this hypothesis, we investigated whether orthovanadate, a known phosphotyrosyl protein phosphatase inhibitor, would mimic fluoride in the stimulation of bone cell proliferation and bone collagen synthesis in vitro. Orthovanadate inhibited the osteoblastic acid phosphatase activity and stimulated bone cell proliferation at the same low concentrations (i.e. 5-15 microM). At the mitogenic doses, orthovanadate also showed a dose-dependent increase in alkaline phosphatase (a marker of mature osteoblasts) in cultured calvarial cells and stimulated bone collagen synthesis, as measured by the incorporation of [3H]proline and the conversion into [3H] hydroxyproline in organ calvaria cultures. Therefore, orthovanadate stimulated bone formation by increasing the number of mature osteoblasts mediated via stimulation of cell proliferation and differentiation. Orthovanadate was dependent on the presence of a mitogen in cell medium for its mitogenic action in vitro and synergistically potentiated the mitogenic actions on osteoblasts of those growth factors, i.e. insulin, epidermal growth factor, insulin-like growth factor I, and skeletal growth factor, whose mitogenic action involved tyrosyl protein phosphorylation. However, the interaction between orthovanadate and basic fibroblast growth factor, a growth factor that does not appear to involve tyrosyl protein phosphorylation, on bone cell proliferation was additive. In summary, these data are consistent with the hypothesis that inhibition of the osteoblastic phosphotyrosyl protein phosphatases can prolong and/or potentiate the mitogenic actions of growth factors, and thereby stimulates cell proliferation.
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PMID:Vanadate stimulates bone cell proliferation and bone collagen synthesis in vitro. 305 61

The gene for Staphylococcal protein A was fused to the coding sequence of bacterial beta-galactosidase, alkaline phosphatase and human insulin-like growth factor I (IGF-I). The fusion proteins, expressed in bacteria, were purified by affinity chromatography on IgG-Sepharose and antibodies were raised in rabbits. All three fusion proteins elicited specific antibodies against both the inserted protein sequences and the protein A moiety. In the case of IGF-I, the protein A moiety in the fusion protein may act as an adjuvant since native IGF-I alone is a poor immunogen. The results suggest that the protein A fusion system can be used for efficient antibody production against peptides or proteins expressed from cloned or synthetic genes. To facilitate such gene fusions a set of optimized vectors have been constructed.
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PMID:Production of specific antibodies against protein A fusion proteins. 309 19

Purified acidic fibroblast growth factor (aFGF) from bovine brain stimulates the proliferation of calvaria-derived osteoblastic cells. Maximum stimulation, relative to corresponding controls, was seen at 0.2% serum (2- to 3-fold), and no stimulation was seen in the absence of serum or under serum replete conditions. The effect was dose-dependent with an ED50 of around 750 pg/ml (47 pM). aFGF (5 ng/ml) sustained the growth of calvaria cells in culture during multiple passages (72 days) at 0.2% serum. In DNA synthesis assays aFGF produced 2- to 4-fold stimulation; insulin-like growth factor I had a slight effect on DNA synthesis on its own, but enhanced the effect of aFGF 2-fold. In cells fully stimulated by epidermal growth factor (5-fold), aFGF had no further effect. Stimulation of DNA synthesis peaked at 5 ng/ml, while higher concentrations were inhibitory. Recombinant aFGF (bovine sequence) also stimulated cell proliferation (1.5-fold), and its potency was augmented by heparin (50 micrograms/ml), about 2-fold. Using simultaneous histochemical staining for alkaline phosphatase activity and [3H]thymidine nuclear uptake we found that aFGF stimulates DNA synthesis to the same extent in alkaline phosphatase-rich (osteoblastic) and alkaline phosphatase-poor (nonosteoblastic) cells. However, after cell division there is a significant decrease in PTH-responsive adenylate cyclase (2- to 3-fold) and in alkaline phosphatase levels (4- to 8-fold). These findings indicate that aFGF is mitogenic to rat calvaria osteoblastic cells, its action requires additional factors, and its growth stimulation is associated with a reduction in phenotypic expression.
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PMID:Growth stimulation of rat calvaria osteoblastic cells by acidic fibroblast growth factor. 367 31

Rat calvaria cells grown in culture for one week had properties of osteoblasts: a high content in alkaline phosphatase and a marked cyclic AMP response to parathyroid hormone (PTH). In short-term experiments, insulin-like growth factor I (IGF I) stimulated the incorporation of [14C] glucose into glycogen. When IGF I was present in the medium during 6 days the cell number increased slightly and there was a substantial, disproportionate rise in alkaline phosphatase activity of the cultures. Thus, IGF I stimulates growth, and in addition, and in contrast to other growth factors, mainly enhances differentiation of osteoblasts.
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PMID:Insulin-like growth factor I supports differentiation of cultured osteoblast-like cells. 608

Bone organ culture makes it possible to observe the direct influence of hormones on bone cells. We studied the effect of growth hormone in vitro on embryonal rat tibiae during culture for 7 days, functionally by measuring the levels of alkaline phosphatase in the culture medium, and morphologically by means of semi-thin sections and electron microscopic examination. Since growth hormone (GH) is supposed to exert an indirect effect on bone cells, somatomedin-C/insulin-like growth factor I (SM-C/IGF I) as a possible mediator was also measured radioimmunologically in the culture medium. In the controls alkaline phosphatase levels showed a continuous increase up to the 7th day which was significantly higher in the presence of GH. There was also a significantly enhanced increase of SM-C/IGF I in the presence of GH during culture in comparison to the controls. Evidently IGF I is produced locally in bone and mediates the effect of GH on bone formation.
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PMID:Effect of growth hormone on osteoblasts and demonstration of somatomedin-C/IGF I in bone organ culture. 638 93

Recent studies have demonstrated that growth hormone (GH)-deficient adults have a markedly decreased bone mineral content compared to healthy adults. However, there are conflicting results regarding the effects of GH treatment on bone mineral content in GH-deficient adults. Therefore, we evaluated the effect of GH treatment on a marker of bone formation (bone alkaline phosphatase), hepatic excretory function and distal forearm bone mineral content in GH-deficient adults. Growth hormone was administered subcutaneously in 21 adults (13 males and 8 females) with GH deficiency of childhood onset for 4 months in a double-blind, placebo-controlled GH trial, while 13 of the patients then received further GH for an additional 14 months. Serum insulin-like growth factor I (IGF-I) increased significantly from 100 to 279 micrograms/l and IGF binding protein-3 (IGFBP-3) from 1930 to 3355 micrograms/l after 4 months of GH treatment (p < 0.0001). In addition, the molar ratio between IGF-I and IGFBP-3 increased significantly from 0.22 to 0.33 after GH treatment (p < 0.0001). Bone alkaline phosphatase increased significantly from 38.6 to 92.9 U/l during GH therapy in male patients (p < 0.0001), whereas liver-derived alkaline phosphatase was unaltered by GH. In the females, the increase in bone alkaline phosphatase did not reach statistical significance (19.1 vs 40.0 U/l, p = 0.06). The GH-induced increase in bone alkaline phosphatase correlated significantly with the increase in serum IGFBP-3 (r = 0.46, p = 0.04) but not with the increase in serum IGF-I (p = 0.16).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Growth hormone (GH) treatment increases serum insulin-like growth factor binding protein-3, bone isoenzyme alkaline phosphatase and forearm bone mineral content in young adults with GH deficiency of childhood onset. 751 28

Bone mineral metabolism and mineralization before and during treatment were studied in 10 girls aged 6.9-8.4 years affected by central precocious puberty and treated with gonadotrophin-releasing hormone agonist (GnRHa) leuprolide acetate depot, in order to understand better the consequences of oestrogen deficiency and the reduction of growth hormone (GH)-insulin-like growth factor I (IGF-I) axis activity. Before and after 12 months of therapy, the patients underwent a clonidine stimulation test and a 4-day calcitriol osteoblast stimulation test. On day 0, day 5 and at 3-month intervals thereafter, serum calcium, phosphate, alkaline phosphatase, IGF-I, IGF binding protein 3 (IGFBP-3), GH, GH binding protein and osteocalcin levels were measured; urinary calcium, phosphate and hydroxyproline levels were evaluated in fasting spot samples. Trabecular and cortical bone mass variations, measured by dual X-ray absorptiometry in the lumbar spine and by dual photon absorptiometry in the radius, respectively were evaluated before the start and after 12 months of therapy. During treatment, a decrease of serum oestradiol levels from pubertal to prepubertal levels was observed. The GH peak following clonidine diminished significantly after 1 year. Growth hormone binding protein showed a slight increase, and IGF-I and IGFBP-3 decreased, although not significantly. Osteocalcin levels decreased significantly after 9 and 12 months of treatment, but they did not change significantly after calcitriol load, either before or after GnRHa therapy. Urinary hydroxyproline decreased significantly after 12 months.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Bone mineral metabolism in girls with precocious puberty during gonadotrophin-releasing hormone agonist treatment. 758 63

In this study we investigated the direct, short-term effects of human growth hormone (hGH) on the biology of normal adult human osteoblast-like (hOB) cells cultured from trabecular bone explants. In Subconfluent cultures, hGH stimulated hOB proliferation in a dose-dependent fashion (P < 0.001, n = 15) with half-maximal effects at a concentration of 10 ng/ml. These mitogenic effects were detectable within 24 hours as shown by bromodeoxyuridine labeling. In confluent cultures containing mainly quiescent cells, hGH increased levels of alkaline phosphatase (P < 0.05, n = 10) and to a lesser degree levels of procollagen type I carboxyterminal propeptide (PICP) (P = 0.07, n = 9). Effects on osteocalcin (bone GLa protein, BGP) levels were highly variable among different cell strains and only 7 of 10 cell strains showed a stimulatory response (P = 0.16). We also studied the effects of hGH on osteoblastic production of insulin-like growth factor I (IGF-I) and IGF-II as well as the production of GH-dependent, insulin-like growth factor binding protein 3 (IGFBP-3). Under basal conditions, human osteoblasts produced IGF-II and IGFBP-3 in the conditioned medium. When stimulated with hGH, minor insignificant increase in both IGF-II and IGFBP-3 (125% and 126% of control, respectively) were detectable. No IGF-I was detectable in the conditioned medium under basal conditions or after stimulation with hGH. In conclusion, the results obtained in this study suggest that GH exerts direct anabolic effects on human osteoblasts.
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PMID:Growth hormone stimulates proliferation and differentiation of normal human osteoblast-like cells in vitro. 768 48


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