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)

Bone tissue has been shown to contain numerous cell-to-cell signaling peptides called growth factors. These growth factors are thought to have important regulating effects for bone remodeling, due to their potent effects on bone cell metabolism. Our investigation was intended to assess the effect of nandrolone decanoate and calcitonin treatment on biochemical markers of bone formation (bone alkaline phosphatase - osteocalcin) and insulin-like growth factor-I in rats. We studied 48 adult male rats. The animals were divided into four groups. Group (A) served as control. Animals in Group (B) were injected with 4 mg/kg/day nandrolone decanoate. Animals in Group (C) were injected with 400mU/rat/day calcitonin and Group (D) received combined therapy for seven days. Nandrolone decanoate and calcitonin have a mild but significant effect on insulin-like growth factor-I without affecting osteocalcin levels, while calcitonin alone decreases the BALP levels. The coadministration of two agents caused notable elevation on insulin-like growth factor-I, followed by a significant increase of osteocalcin and bone alkaline phosphatase.
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PMID:Interaction between nandrolone decanoate and calcitonin in bone formation markers (osteocalcin and bone specific alkaline phosphatase) and IGF-I in rats. 1575 66

In the present study, we investigated whether Akt is involved in insulin-like growth factor-I (IGF-I)-stimulated activity of alkaline phosphatase, a marker of mature osteoblast phenotype, in osteoblast-like MC3T3-E1 cells. IGF-I induced the phosphorylation of Akt in these cells. Akt inhibitor significantly suppressed the IGF-I-stimulated alkaline phosphatase activity. The phosphorylation of Akt induced by IGF-I was reduced by the Akt inhibitor. LY294002 and wortmannin, inhibitors of phosphatidylinositol 3-kinase, significantly suppressed the IGF-I-induced alkaline phosphatase activity. The phosphorylation of Akt induced by IGF-I was markedly reduced by LY294002 and wortmannin. These results strongly suggest that phosphatidylinositol 3-kinase/Akt plays a role in the IGF-I-stimulated alkaline phosphatase activity in osteoblasts.
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PMID:Possible involvement of phosphatidylinositol 3-kinase/Akt pathway in insulin-like growth factor-I-induced alkaline phosphatase activity in osteoblasts. 1597 Nov 48

The role of regucalcin in the regulation of osteoblastic cell function was investigated. Osteoblastic MC3T3-E1 cells with subconfluent monolayers were cultured in a medium containing regucalcin (10(-10)-10(-8) M) without fetal bovine serum (FBS). The proliferation of osteoblastic cells was not significantly altered in the presence of regucalcin. The results of reverse transcription-polymerase chain reaction (RT-PCR) analysis with specific primers showed that the expression of Runx2 (Cbfa1) and insulin-like growth factor-I (IGF-I) mRNAs in osteoblastic cells was significantly suppressed in the presence of regucalcin (10(-10) or 10(-9) M). Transforming growth factor-beta1 mRNA levels were significantly enhanced in the 24 h-culture with regucalcin (10(-10) or 10(-9) M). Alpha1(I) collagen and glyceroaldehyde-3-phosphate dehydrogenase (G3PDH) mRNA levels were not significantly changed by culture with regucalcin (10(-10) or 10(-9) M). Alkaline phosphatase activity was significantly decreased in the lysate of cells cultured for 24 or 48 h with regucalcin (10(-10)-10(-8) M). Moreover, the expression of regucalcin in osteoblastic cells was demonstrated by RT-PCR and Western blot analysis. When regucalcin (10(-7) M) was added into the enzyme reaction mixture containing the lysate of osteoblastic cells cultured in the absence of regucalcin, alkaline phosphatase activity was significantly decreased. Also, Ca2+/calmodulin-dependent nitric oxide (NO) synthase activity in the cell lysate was significantly decreased by addition of regucalcin (10(-10)-10(-8) M) into the reaction mixture. The presence of anti-regucalcin monoclonal antibody (5 or 10 ng/ml) in the enzyme reaction mixture caused a significant increase in NO synthase activity in the cell lysate in the presence or absence of Ca2+/calmodulin, suggesting a role of endogenous regucalcin. When osteoblastic cells with subconfluency were cultured in the presence of regucalcin (10(-10) or 10(-9) M) for 3, 9, or 18 days, the results with Alizarin red staining showed that the mineralization was markedly suppressed by culture with regucalcin for 3, 9, or 18 days. This study demonstrates that regucalcin regulates the function of osteoblastic cells, and that the protein suppresses cell differentiation and mineralization.
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PMID:Suppressive effect of regucalcin on cell differentiation and mineralization in osteoblastic MC3T3-E1 cells. 1605 80

Tissue formation and repair are dependent upon cascades of biological events, but the signals involved and the possible gene coexpression patterns during intramembranous bone repair are only poorly understood. We sought to place this mode of regeneration in context by profiling quantitative gene expression for a panel of 39 genes between days 1 and 14 following rat femoral marrow ablation. In situ hybridization was employed to localize a subset of genes. Additionally, principal components analysis was conducted to identify underlying factors suggestive of coexpression patterns. During inflammation (days 1-5), several genes, including cyclooxygenase-1 and -2, showed downregulation. Other proinflammatory cytokines, tumor necrosis factor-alpha and interleukin-1beta, exhibited increasing levels around day 5. During repair (days 3-10), growth factors, receptors, and inhibitor genes for transforming growth factor- beta; basic fibroblast growth factor; bone morphogenetic proteins 2, 4, and 7; vascular endothelial growth factor; and insulin-like growth factor-I were upregulated. In addition, the gene for core binding factor-alpha1 and markers of osteoblast function such as alkaline phosphatase, collagen type I, osteonectin, osteopontin, and osteocalcin had peak expression at day 5 or 7. The remodeling phase (days 10-14) was characterized by peaks for cytokines associated with osteoclastic activity including receptor activator of nuclear factor-kappaB, receptor activator of nuclear factor-kappaB ligand (RANKL), cathepsin K, tumor necrosis factor-alpha, interleukin-6, and cyclooxygenase-2. In situ hybridization showed that the most common sites of increased signal were within osteoblastic cells on trabecular and endosteal surfaces. Principal components analysis identified eight underlying factors that together explained over 80% of the variance in the data.
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PMID:Patterns and localization of gene expression during intramembranous bone regeneration in the rat femoral marrow ablation model. 1619 34

The bone metabolic processes of proliferation and differentiation in preterm and term newborns have yet to be fully elucidated. Seventy-four umbilical cord blood samples were collected from preterm and term newborns delivered at 27 to 42 gestational weeks (GWs). Carboxy-terminal propeptide of type I procollagen (PICP), pyridinoline cross-linked telopeptide domain of type I collagen (ICTP), alkaline phosphatase (ALP), and bone-specific alkaline phosphatase (BAP) were measured. Calcitonin (CT), estrogen (E2), intact parathyroid hormone, and insulin-like growth factor-I (IGF-I) were also examined in 20 or 23 randomly selected samples. We conducted cross-sectional regression analyses for bone metabolic markers, fetal growth markers including GWs, birth weight (BW), height (BH) and head circumference (HC), and bone related hormones. PICP and ICTP activities were very high, but decreased significantly with fetal growth based on GWs, BW, BH, and HC changes (GWs, BW, and BH to both PICP and ICTP, P < 0.0001; HC to ICTP, P < 0.0001; HC to PICP, P < 0.05), while BAP and ALP did not change significantly. E2 and CT both showed a significant positive correlation with Ca (P < 0.05), but neither hormone had any apparent correlation with PICP, ALP, BAP, or ICTP. These results suggest very active bone formation and resorption of type I collagen to be dependent on fetal growth and that fetal osteoblasts dominate the proliferation phase of development rather than the maturation phase. However, factors contributing to high bone turnover in the fetus remain to be elucidated.
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PMID:High bone turnover of type I collagen depends on fetal growth. 1621 33

Acromegaly is a rare disease caused by growth hormone (GH) hypersecretion. GH and insulin-like growth factor-I (IGF-I) exert anabolic activity in bones. Nevertheless, bone mineral density (BMD) loss is not uncommon in patients with acromegaly. It is assumed to be due to hypogonadism associated with the acromegaly. The aim of the study was to examine BMD at various skeletal sites and bone turnover and to assess the influence of impaired gonadal function and disease activity on BMD and turnover changes in acromegaly. A total of 62 patients were studied (40 women, 22 men). Among the women, 22 had active disease and 18 were cured; 16 women had normal gonadal function, and 24 were hypogonadal. Altogether, 12 men presented with active acromegaly, and 10 were cured; normal gonadal function was found in 10 men, and hypogonadism was diagnosed in 12 men. Controls were 30 healthy subjects. Densitometry using dual-energy X-ray absorptiometry of the lumbar spine, proximal femur, forearm, and total body was carried out. Bone turnover was studied based on serum osteocalcin, C-terminal collagen type 1 crosslinks, and bone alkaline phosphatase concentration. A disadvantageous effect of acromegaly on bone density was associated with hypogonadism in the distal radius (in women), the proximal femur (in men), and the total body (both sexes). An anabolic effect of GH during active acromegaly was present in the proximal femur only in men. We confirmed increased bone turnover in the presence of acromegaly, and these changes were similar regarding the activity of the disease and the gonadal status.
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PMID:Bone mineral density and turnover in patients with acromegaly in relation to sex, disease activity, and gonadal function. 1636 2

This study evaluated the effect of a fat blend containing long-chain (LC) n-3 PUFA on bone mineral density (BMD) and bone metabolism in gonad-intact middle-aged male rats (12 months old, n 28). Seven rats were killed on day 0 of dietary intervention to determine the baseline BMD. The remaining rats (seven per group) were fed a diet with one of the following dietary lipid treatments (g/kg diet): 167 g safflower oil + 33 g menhaden oil (N6 + N3 diet, control), 200 g safflower oil (N6 diet, almost devoid of LC n-3 PUFA), or 190 g menhaden oil + 10 g corn oil (N3 diet, rich in LC n-3 PUFA) for 20 weeks. After 20 weeks, all dietary treatment groups had a lower BMD compared with the baseline reference. However, rats fed the N3 diet had the highest bone mineral content and cortical + subcortical BMD compared with those fed the N6 and control N6 + N3 diet. Compared with the control (N6 + N3) group, rats fed the N3 diet had higher values for serum insulin-like growth factor-I, parathyroid hormone, 1,25-(OH)2 vitamin D3 and bone-specific alkaline phosphatase activity, but lower bone NO production and urinary Ca, whereas rats fed the N6 diet had higher bone prostaglandin E2 production and serum pyridinoline. These findings indicate a protective action of LC n-3 PUFA on ageing-induced bone loss in gonad-intact middle-aged male rats through a modulation of local factors and systemic calcitrophic hormones.
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PMID:Protective effect of dietary long-chain n-3 polyunsaturated fatty acids on bone loss in gonad-intact middle-aged male rats. 1651 31

It has been shown that insulin-like growth factor-I (IGF-I) stimulates the activity of alkaline phosphatase, a marker of mature osteoblast phenotype, in osteoblasts. In the present study, we investigated the involvement of the mitogen-activated protein (MAP) kinase superfamily in the IGF-I-stimulated alkaline phosphatase activity in osteoblast-like MC3T3-E1 cells. IGF-I-stimulated alkaline phosphatase activity dose dependently in the range between 1 nM and 0.1 microM. IGF-I induced the phosphorylation of p44/p42 MAP kinase and p38 MAP kinase but not stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK). PD98059 and U0126, specific inhibitors of the upstream kinase that activates p44/p42 MAP kinase, significantly suppressed the IGF-I-induced alkaline phosphatase activity. On the contrary, SB203580 and PD169316, specific inhibitors of p38 MAP kinase, failed to affect the activity induced by IGF-I. Specific inhibitors for phosphatidylinositol 3-kinase (PI3K)/Akt pathway (LY294002 and wortmannin) also had no significant effect on IGF-I-induced p44/p42 MAP kinase phosphorylation. The phosphorylation of p44/p42 MAP kinase induced by IGF-I was reduced by U0126. These results strongly suggest that p44/p42 MAP kinase among the MAP kinase superfamily plays a role in the IGF-I-stimulated alkaline phosphatase activity in osteoblast-like MC3T3-E1 cells.
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PMID:Involvement of p44/p42 MAP kinase in insulin-like growth factor-I-induced alkaline phosphatase activity in osteoblast-like-MC3T3-E1 cells. 1661 13

Severe short stature resulting from a deficiency in insulin-like growth factor-I (IGF-I) is a prominent feature of Laron syndrome (LS). Whether patients with LS are osteopenic or not, and whether they need treatment with bisphosphonates, remains uncertain. The aim of this study was to investigate the action of alendronate on the IGF-I-deficient bones of adult patients with LS and osteoporosis, as determined by dual X-ray absorptiometry . Seven patients (5 women and 2 men) of mean age 40.8+/-7.6 years and mean bone mass density (BMD) 0.843+/-0.06 g/cm2 (T score -2.9+/-0.5) at the lumbar spine and 0.734+/-0.11 g/cm2 (T score -2.2+/-0.9) at the femoral neck were treated with alendronate 70 mg once/weekly over a 12-month period. Treatment led to an increase of 5.3% in BMD (p=0.038) at the femoral neck. There was a similar trend at the lumbar spine, but the difference was not statistically significant (2.3%, p=0.34). Mean total alkaline phosphatase decreased by 14% from normal range at baseline (p=0.007). Urinary deoxypyridinoline levels, which were elevated at baseline (10+/-2.3 nM/mMcre), showed a nonsignificant change during treatment. Our study suggests that treatment with alendronate may have positive effects in patients with LS and low BMD on dual X-ray absorptiometry.
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PMID:Effect of alendronate on bone mineral density in adult patients with Laron syndrome (primary growth hormone insensitivity). 1661 31

Bone loss is induced in regucalcin transgenic rats. The role of exogenous regucalcin in the regulation of osteoblastic cell function was investigated. Osteoblastic MC3T3-E1 cells with subconfluent monolayers were cultured for 24-72 h in medium containing regucalcin (10(-10) or 10(-9) M) without fetal bovine serum. The presence of regucalcin did not have a significant effect on cell number. Culture with regucalcin (10(-9) M) for 24 h caused a significant decrease in protein and DNA contents in osteoblastic cells. The effect of regucalcin in decreasing cellular protein content was significantly inhibited in the presence of various kinase inhibitors including staurosporine (10(-7) M), dibucaine (10(-6) M), PD98059 (10(-8) M), or wortmannin (10(-8) M). Meanwhile, culture with regucalcin caused a significant decrease in cellular DNA content in the presence of various kinase inhibitors. The presence of regucalcin did not have a significant effect on protein and DNA contents in the cells cultured with cycloheximide (10(-7) M), an inhibitor of protein synthesis, or 5,6-dichloro -1-beta-D-ribofuranosylbenzimidazole (10(-6) M), an inhibitor of transcription activity; which each inhibitor caused a significant decrease in those contents. The effect of regucalcin in decreasing cellular protein content was seen in the presence of insulin-like growth factor-I (IGF-I; 10(-9) or 10(-8) M). Such an effect was not observed in cellular DNA content. The results of reverse transcription-polymerase chain reaction analysis with specific primers showed that the expression of Runx 2 (Cbfa 1) and alkaline phosphatase mRNAs in osteoblastic cells was significantly suppressed in the presence of regucalcin (10(-10) or 10(-9) M). Glyceraldhyde-3-phosphate dehydrogenase mRNA level was not significantly changed with culture of regucalcin (10(-10) or 10(-9) M). This study supports the view that exogenous regucalcin regulates the function of osteoblastic cells, and that the effect of protein is mediated through signaling factors.
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PMID:Regulatory effect of exogenous regucalcin on cell function in osteoblastic MC3T3-E1 cells: involvement of intracellular signaling factor. 1682 Sep 41


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