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 effect of menaquinone-7 (MK-7) on bone components and bone resorbing factors induced-bone resorption using the femoral-diaphyseal and - metaphyseal tissues obtained from elderly female rats in vitro were examined. Calcium content, alkaline phosphatase activity and deoxyribonucleic acid (DNA) in the diaphyseal and metaphyseal tissues in elderly females rats were significantly decreased as compared with that of young rats, indicating that aging causes a deterioration of bone formation. The presence of MK-7 (10(-6)-10(-5) M) caused a significant prevention of reduction of biochemical components. On the other hand, the bone-resorbing factor, parathyroid hormone (1-34) (PTH; 10(-7) M) and prostaglandin E(2) (PGE(2); 10(-5) M) caused a significant decrease in calcium content in the diaphyseal and metaphyseal tissues. This decreases was completely inhibited in the presence of MK-7 (10(-7)-10(-5) M). In addition, MK-7 (10(-7)-10(-5) M) completely prevented the PTH (10(-7) M) or PGE(2) (10(-5) M) induced increases in medium glucose consumption and lactic acid production by bone tissues, Furthermore, the effect of the prolonged intake of dietary MK-7 on bone loss in ovariectomized rats was investigated. As a result, it was found that the intake of experimental diets containing the fermented soybean (natto) with supplemental MK-7 caused significant elevations of MK-7 and gamma-carboxylated osteocalcin concentration, a bio marker of bone formation, in the serum of both ovariectomized rats and normal subjects, suggesting that MK-7 may play an important role in the prevention of age-related bone loss.
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PMID:Studies on action of menaquinone-7 in regulation of bone metabolism and its preventive role of osteoporosis. 1563 Feb 45

Previous studies have indicated that one of the causes of alveolar bone destruction with periodontitis is lipopolysaccharide (LPS) from the cell wall of gram-negative bacteria in plaque, and that prostaglandin E(2) (PGE(2)) is one of the bone resorption factors that stimulate osteoclast formation through an intercellular interaction between osteoblasts and osteoclast precursors. The present study was undertaken to determine the effect of LPS on cell growth, alkaline phosphatase (ALPase) activity, the production of PGE(2), and the expression of receptors by PGE(2), cyclooxygenase (COX)-1, and COX-2, using human osteosarcoma cell line Saos-2 as osteoblasts. The cells were cultured with 0, 1, or 10 microg mL(-1) of LPS for up to 14 days. The production of PGE(2) and the gene expression of COX-1, COX-2, and PGE(2) receptors, including Ep1, Ep2, Ep3, and Ep4, were determined using enzyme-linked immunosorbent assay (ELISA) and real-time reverse transcription-polymerase chain reaction (real-time RT-PCR), respectively. With the addition of LPS, cell growth and ALPase activity decreased by day 5 of the culture, while PGE(2) production increased in a dose-dependent manner throughout the entire 14-day culture period. LPS-reduced ALP activity and LPS-induced PGE(2) production returned to the control level by the addition simultaneously with indomethacin. The expression of COX-1, Ep1, Ep2, and Ep3 receptors decreased on day 14 of the culture, whereas the expression of COX-2 and Ep4 receptors increased significantly with the addition of LPS. These results suggest that LPS promotes PGE(2) production by increasing the expression of COX-2, and that LPS promotes the production of Ep4 receptors in osteoblasts. These results also indicate that LPS-induced PGE(2) may combine with osteoblast Ep4 receptors in autocrine or paracrine modes, and may promote the formation of osteoclasts.
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PMID:Lipopolysaccharide stimulates the production of prostaglandin E2 and the receptor Ep4 in osteoblasts. 1628 20

The biological activities of parathyroid hormone (PTH) on bone are quite complex as demonstrated by its catabolic and anabolic activities on the skeleton. Although there have been many reports describing genes that are regulated by PTH in osteoblast cells, the goal of this study was to utilize a well-established in vivo PTH anabolic treatment regimen to identify genes that mediate bone anabolic effects of PTH. We identified a gene we named PTH anabolic induced gene in bone (PAIGB) that has been reported as brain and acute leukemia cytoplasmic (BAALC). Therefore, using the latter nomenclature, we have discovered that BAALC is a PTH-regulated gene whose mRNA expression was selectively induced in rat tibiae nearly 100-fold (maximal) by a PTH 1-34 anabolic treatment regimen in a time-dependent manner. Although BAALC is broadly expressed, PTH did not regulate BAALC expression in other PTH receptor expressing tissues and we find that the regulation of BAALC protein by PTH in vivo is confined to mature osteoblasts. Further in vitro studies using rat UMR-106 osteoblastic cells show that PTH 1-34 rapidly induces BAALC mRNA expression maximally by 4 h while the protein was induced by 8 h. In addition to being regulated by PTH 1-34, BAALC expression can also be induced by other bone forming factors including PGE(2) and 1,25 dihydroxy vitamin D(3). We determined that BAALC is regulated by PTH predominantly through the cAMP/PKA pathway. Finally, we demonstrate in MC3T3-E1 osteoblastic cells that BAALC overexpression regulates markers of osteoblast differentiation, including downregulating alkaline phosphatase and osteocalcin expression while inducing osteopontin expression. We also demonstrate that these transcriptional responses mediated by BAALC are similar to the responses elicited by PTH 1-34. These data, showing BAALC overexpression can mimic the effect of PTH on markers of osteoblast differentiation, along with the observations that BAALC is induced selectively with a bone anabolic treatment regimen of PTH (not a catabolic treatment regimen), suggest that BAALC may be an important mediator of the PTH anabolic action on bone cell function.
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PMID:Identification of a PTH regulated gene selectively induced in vivo during PTH-mediated bone formation. 1651 68

We compared the direct effects of selective EP4 and EP2 receptor agonists (EP4A and EP2A) with prostaglandin E(2) (PGE(2)) on the differentiation of cultured murine calvarial osteoblastic cells. EP4A increased alkaline phosphatase activity and osteocalcin mRNA levels in these cultures similar to PGE(2). This effect was seen with both "direct plating" immediately after isolating the cells, or "indirect plating" in which the cells were grown to confluence and replated. EP2A had a smaller effect, significant only in "indirect plating" experiments. All three agents decreased the DNA and protein content in indirect plating experiments, but not in direct plating experiments. We conclude that the anabolic effect of PGE(2) in calvarial osteoblastic cell cultures is largely mediated by activation of the EP4 receptor, while activation of the EP2 receptor is less effective.
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PMID:Effects of selective prostaglandins E2 receptor agonists on cultured calvarial murine osteoblastic cells. 1708 26

Osteoblasts are exposed to fluid shear in vivo but the effects are not well understood, particularly how substrate properties or length of exposure modify the response. Short exposure (1 h) to shear reduces the stimulatory effect of micron-scale surface structure on osteoblast differentiation, but the effects of longer term exposures are not known. To test the hypothesis that substrate-dependent responses of osteoblasts to shear depend on the length of exposure to fluid flow, MG63 osteoblasts were grown on tissue culture glass, which has an average roughness (Ra) < 0.2 microm; machined Ti disks (PT, Ra < 0.6 microm); Ti disks with a complex microarchitecture [sand blasted acid etched (SLA), Ra = 4-5 microm); and Ti plasma-sprayed surfaces [Ti via plasma spray (TPS), Ra = 7 microm]. Confluent cultures were exposed to pulsatile flow at shear forces of 0, 1, and 14 dynes/cm(2) for 0, 6, 12, and 24 h. Shear reduced cell number on all surfaces, with greatest effects on TPS. Shear had no effect on alkaline phosphatase on smooth surfaces but increased enzyme activity on SLA and TPS in a time-dependent manner. Its effects on osteocalcin, TGF-beta1, and PGE(2) in the conditioned media were greatest on these surfaces as well. Responses to fluid-induced shear were blocked by the general Cox inhibitor indomethacin and the Cox-2 inhibitor meloxicam, indicating that response to shear is mediated by prostaglandin produced via a Cox-2 dependent mechanism. These results show that the effects of fluid induced shear change with time and are substrate dependent, suggesting that substrate microarchitecture regulates the osteoblast phenotype and effects of shear are determined by the maturation state of the responding population.
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PMID:Osteoblast response to fluid induced shear depends on substrate microarchitecture and varies with time. 1734 Jun

Previous studies have indicated that lipopolysaccharide (LPS) from Gram-negative bacteria in plaque induces the release of prostaglandin E(2) (PGE(2)), which promotes alveolar bone resorption in periodontitis, and that tobacco smoking might be an important risk factor for the development and severity of periodontitis. We determined the effect of nicotine and LPS on alkaline phosphatase (ALPase) activity, PGE(2) production, and the expression of cyclooxygenase (COX-1, COX-2), PGE(2) receptors Ep1>4, and macrophage colony stimulating factor (M-CSF) in human osteoblastic Saos-2 cells. The cells were cultured with 10(-3) M nicotine in the presence of 0, 1, or 10 mug/ml LPS, or with LPS alone. ALPase activity decreased in cells cultured with nicotine or LPS alone, and decreased further in those cultured with both nicotine and LPS, whereas PGE(2) production significantly increased in the former and increased further in the latter. By itself, nicotine did not affect expression of COX-1, COX-2, any of the PGE(2) receptors, or M-CSF, but when both nicotine and LPS were present, expression of COX-2, Ep3, Ep4, and M-CSF increased significantly. Simultaneous addition of 10(-4) M indomethacin eliminated the effects of nicotine and LPS on ALPase activity, PGE(2) production, and M-CSF expression. Phosphorylation of protein kinase A was high in cells cultured with nicotine and LPS. These results suggest that LPS enhances the production of nicotine-induced PGE(2) by an increase in COX-2 expression in osteoblasts, that nicotine-LPS-induced PGE2 interacts with the osteoblast Ep4 receptor primarily in autocrine or paracrine mode, and that the nicotine-LPS-induced PGE(2) then decreases ALPase activity and increases M-CSF expression.
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PMID:Lipopolysaccharide enhances the production of nicotine-induced prostaglandin E2 by an increase in cyclooxygenase-2 expression in osteoblasts. 1734 54

The effects of luteolin on the function of osteoblastic MC3T3-E1 cells and the production of local factors in osteoblasts were investigated. Luteolin (1microM) caused a significant elevation of collagen content, alkaline phosphatase (ALP) activity, and osteocalcin secretion in the cells (P<0.05). The effect of luteolin in increasing collagen content and ALP activity was completely prevented by the presence of 10(-6)M cycloheximide and 10(-6)M tamoxifen, suggesting that luteolin's effect results from a newly synthesized protein component and might be partly involved in estrogen action. We then examined the effect of luteolin on the 3-morpholinosydnonimine (SIN-1)-induced production of oxidative stress markers [nitric oxide (NO) and prostaglan E(2) (PGE(2))] and cytokines [tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6)] in osteoblasts. Luteolin (1 and 10microM) decreased the SIN-1-induced production of NO, PGE(2), TNF-alpha, and IL-6 in osteoblasts. These results suggest that inflammatory mediators can be regulated by luteolin stimulating osteoblastic function.
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PMID:Modulatory effects of luteolin on osteoblastic function and inflammatory mediators in osteoblastic MC3T3-E1 cells. 1736 35

Cyclooxygenase-2 (COX-2) is highly expressed in osteoblasts, and COX-2 produced prostaglandins (PGs) can increase osteoblastic differentiation in vitro. The goal of this study was to examine effects of COX-2 expression on calvarial osteoblastic proliferation and apoptosis. Primary osteoblasts (POBs) were cultured from calvariae of COX-2 wild-type (WT) and knockout (KO) mice. POB proliferation was evaluated by (3)H-thymidine incorporation and analysis of cell replication and cell cycle distribution by flow cytometry. POB apoptosis was evaluated by annexin and PI staining on flow cytometry. As expected, PGE(2) production and alkaline phosphatase (ALP) activity were increased in WT cultures compared to KO cultures. In contrast, cell numbers were decreased in WT compared to KO cells by day 4 of culture. Proliferation, measured on days 3-7 of culture, was 2-fold greater in KO than in WT POBs and associated with decreased Go/G1 and increased S cell cycle distribution. There was no significant effect of COX-2 genotype on apoptosis under basal culture conditions on day 5 of culture. Cell growth was decreased in KO POBs by the addition of PGE(2) or a protein kinase A agonist and increased in WT POBs by the addition of NS398, a selective COX-2 inhibitor. In contrast, differentiation and cell growth in marrow stromal cell (MSC) cultures, evaluated by ALP and crystal violet staining respectively, were increased in MSCs from WT mice compared to MSCs from KO mice, and exogenous PGE(2) increased cell growth in KO MSC cultures. We conclude that PGs secondary to COX-2 expression decrease osteoblastic proliferation in cultured calvarial cells but increase growth of osteoblastic precursors in MSC cultures.
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PMID:Cyclooxygenase-2 gene disruption promotes proliferation of murine calvarial osteoblasts in vitro. 1746 56

Adipose tissue-derived mesenchymal stem cells (AT-MSCs) are currently used for bone tissue engineering. AT-MSCs undergoing osteogenic differentiation respond to mechanical loading with increased cyclooxygenase-2 gene expression, a key enzyme in prostaglandin (PG) synthesis. PGs are potent multifunctional regulators in bone, exhibiting stimulatory and inhibitory effects on bone formation and resorption. PGE(2), but not PGI(2) or PGF(2), recruits osteoprogenitors from the bone marrow space and influences their differentiation. We hypothesize that PGE(2), PGI(2), and PGF(2) may differentially regulate osteogenic differentiation of human AT-MSCs. PGE(2), PGI(2), and PGF(2) (0.01-10 microM) affected osteogenic differentiation, but not proliferation of AT-MSCs after 4-14 days. Only PGF(2) (0.01-10 microM) increased alkaline phosphatase (ALP) activity at day 4. PGE(2) (10 microM), PGI(2) (0.01-10 microM), and PGF(2) (10 microM) decreased ALP activity, whereas PGF(2) (0.1 microM) increased ALP activity at day 14. PGF(2) (0.01-0.1 microM) and PGI(2) (0.01 microM) upregulated osteopontin gene expression, and PGF(2) (0.01 microM) upregulated alpha1(I)procollagen gene expression at day 4. PGE(2) and PGF(2) (10 microM) at day 4 and PGF(2) (1 microM) at day 14 downregulated runt-related transcription factor-2 gene expression. We conclude that PGE(2), PGI(2), and PGF(2) differentially affect osteogenic differentiation of AT-MSCs, with PGF(2) being the most potent. Thus, locally produced PGF(2) might be most beneficial in promoting osteogenic differentiation of AT-MSCs, resulting in enhanced bone formation for bone tissue engineering.
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PMID:Prostaglandins differentially affect osteogenic differentiation of human adipose tissue-derived mesenchymal stem cells. 1765 90

We use an in-vitro osteoblast cell culture model to investigate the effects of low-frequency (7.5 Hz) pulsed electromagnetic field (PEMF) stimulation on osteoblast population, cytokines (prostaglandin E(2) (PGE(2)), transforming growth factor beta1(TGFbeta1), and alkaline phosphatase (ALP) activity to find the optimal intensity of PEMF for osteoblast growth. The results demonstrate that PEMF can stimulate osteoblast growth, release of TGFbeta1, and, in addition, an increase of ALP activity. The synthesis and release of PGE(2) in the culture medium are reduced with increasing numbers of cells. Higher intensity does not necessarily mean increased osteoblast growth, and the most efficient intensity is about 2 mV/cm in this case. Although the lower intensities of the PEMF are yet to be determined, the results of this study can shed light on the mechanisms of PEMF stimulation on non union fracture therapy and osteoporosis prevention in the future.
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PMID:Cytokine release from osteoblasts in response to different intensities of pulsed electromagnetic field stimulation. 1788 3


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