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 effects of cAMP and cGMP on the differentiation of osteoblast-like cells derived from rat calvariae and on the formation of bone in vitro were studied. Continuous culture of osteoblast-like cells in the presence of 8-bromo-cyclic AMP (8-Br-cAMP) resulted in the dose-related inhibition both of the synthesis of cellular alkaline phosphatase (ALPase), which is known as a marker of osteoblastic differentiation, and of the formation of mineralized nodules, which is a model of the formation of bone in vitro. By contrast, 8-bromo-cyclic GMP (8-Br-cGMP) promoted the synthesis of ALPase and the formation of mineralized nodules. Northern blot analysis revealed that these cyclic nucleotides modulated the steady-state levels of mRNAs for ALPase and osteocalcin, a bone-matrix protein that is specifically produced by osteoblast. The present results indicate that cAMP and cGMP act reciprocally to regulate osteoblastic differentiation and the subsequent formation of mineralized nodules.
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PMID:Reciprocal regulation by cyclic nucleotides of the differentiation of rat osteoblast-like cells and mineralization of nodules. 748 37

Monoclonal antibodies (MAbs) were raised against the gag protein of human immunodeficiency virus type 1 (HIV-1). The reactivity of the selected Mabs with the matrix protein p17 of HIV-1 were investigated in several tests, i.e. ELISA, immunostaining of Western blots, and alkaline phosphatase anti-alkaline phosphatase immunocytochemistry (APAAP). All three Mabs reacted exclusively with HIV-1 and showed specific binding to the virus surface in pre-embedding immuno-electron-microscopy and useful as diagnostic agents. In an "in vitro" cultivation experiment the MAbs showed antiviral activity in concentrations in the range of 25-100 micrograms/ml. No binding region could be defined using overlapping peptides consisting of the p17 protein sequence of HIV-1 in an epitope mapping system and therefore we concluded, that the MAbs recognize a conformational epitope.
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PMID:Characterization of murine monoclonal antibodies directed against the submembrane protein p17 of HIV-1. 750 41

Tetranectin is a protein shared by the blood and the extracellular matrix. Tetranectin is composed of four identical, noncovalently bound polypeptides each with a molecular mass of approximately 21 kD. There is some evidence that tetranectin may be involved in fibrinolysis and proteolysis during tissue remodeling, but its precise biological function is not known. Tetranectin is enriched in the cartilage of the shark, but the gene expression pattern in the mammalian skeletal system has not been determined. In the present study we have examined the expression pattern and putative function of tetranectin during osteogenesis. In the newborn mouse, strong tetranectin immunoreactivity was found in the newly formed woven bone around the cartilage anlage in the future bone marrow and along the periosteum forming the cortex. No tetranectin immunoreactivity was found in the proliferating and hypertrophic cartilage or in the surrounding skeletal muscle. Using an in vitro mineralizing system, we examined osteoblastic cells at different times during their growth and differentiation. Tetranectin mRNA appeared in the cultured osteoblastic cells in parallel with mineralization, in a pattern similar to that of bone sialoprotein, which is regarded as one of the late bone differentiation markers. To explore the putative biological role of tetranectin in osteogenesis we established stably transfected cell lines (PC12-tet) overexpressing recombinant tetranectin as evidenced by Northern and Western blot analysis and immunoprecipitation. Both control PC12 cells and PC12-tet cells injected into nude mice produced tumors containing bone material, as evidenced by von Kossa staining for calcium and immunostaining with bone sialoprotein and alkaline phosphatase antiserum. Nude mice tumors established from PC12-tet cells contained approximately fivefold more bone material than those produced by the untransfected PC12 cell line or by the PC12 cells transfected with the expression vector with no insert (Mann Whitney rank sum test, p < 0.01), supporting the notion that tetranectin may play an important direct and/or indirect role during osteogenesis. In conclusion, we have established a potential role for tetranectin as a bone matrix protein expressed in time and space coincident with mineralization in vivo and in vitro.
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PMID:A potential role for tetranectin in mineralization during osteogenesis. 779 25

Treatment of mouse MC3T3-E1 cells with ascorbic acid initiates the formation of a collagenous extracellular matrix and synthesis of several osteoblast-related proteins. We recently showed that ascorbic acid dramatically increases alkaline phosphatase and osteocalcin mRNAs and that this induction is blocked by inhibitors of collagen triple-helix formation (Franceschi and Iyer, J Bone Miner Res 7:235). In the present study, the relationship between collagen matrix formation and osteoblast-specific gene expression is explored in greater detail. Kinetic studies revealed that ascorbic acid increased proline hydroxylation in the intracellular procollagen pool within 1 h and stimulated the cleavage of type I collagen propeptides beginning at 2.5 h. Mature alpha 1(I) and alpha 2(I) collagen components were first detected at 10 h and continued to increase in both cell layer and culture medium for up to 72 h. Ascorbic acid also increased the rate of procollagen secretion from cell layers to culture medium. The secretion of another matrix protein, fibronectin, was only slightly affected. Alkaline phosphatase or its mRNA was first detected 2-3 days after ascorbic acid addition, but osteocalcin mRNA was not seen until day 6. Two inhibitors of collagen triple-helix formation, ethyl-3,4-dihydroxybenzoate and 3,4-dehydroproline, inhibited procollagen hydroxylation and alkaline phosphatase induction. 3,4-Dehydroproline also inhibited the induction of alkaline phosphatase and osteocalcin mRNAs. Surprisingly, induction was not blocked if cells were exposed to ascorbic acid before inhibitor addition. Alkaline phosphatase was also partially inhibited if cells were grown in the presence of purified bacterial collagenase. These results indicate that the induction of osteoblast markers by ascorbic acid does not require the continuous hydroxylation and processing of procollagens and suggest that a stable, possibly matrix-associated signal is generated at early times after ascorbic acid addition that allows subsequent induction of osteoblast-related genes.
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PMID:Effects of ascorbic acid on collagen matrix formation and osteoblast differentiation in murine MC3T3-E1 cells. 807 60

Two matched groups of postmenopausal patients were treated respectively with calcitonin or calcitonin and an arginine-lysine-glycerophosphoric acid-lactose association. The rationale underlying this therapy took the form of data in the literature which indicated an action of these amino acids and lactose on calcium absorption and on the metabolism of protein components in the skeletal structure. The following tests were performed: mineralometric evaluation, evaluation of painful symptoms and intake of pain-relieving drugs, serum levels of calcium, phosphorus, alkaline phosphatase, osteocalcin, parathormone, and calciuria and hydroxyproline. These parameters were assayed at the beginning and end of treatment which lasted six months. The results, or in other words the comparison between the two groups, basal or after treatment, and the values recorded before and after treatment in each group, enable the authors to affirm that the administration of the arginine-lysine-glycerophosphoric acid-lactose association leads to an increase in bone density and plasma osteocalcin, a reduction in painful symptoms and analgesic intake, and a reduction in the serum levels of parathromone and hydroxyproline. Data reported in the literature support the conclusion that the results obtained are the consequence of an improved intestinal absorption calcium. It is highly probable that the protein components of the association administered, arginine-lysine-glycerophosphoric acid-lactose, also exercise a direct action on osteoblasts and on the metabolism of bone matrix protein components.
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PMID:[Experience regarding the use of arginine-lysine-lactose treatment in menopausal osteoporosis]. 808 36

Estrogens play an important but poorly understood role in the maintenance of skeletal mass. Whereas the mechanisms of estrogen action on bone may be complex, the finding that osteoblasts express estrogen receptors suggests that this class of hormones exerts direct effects on bone cells. To understand how estrogens regulate osteoblastic function, the physiologically active estrogen metabolite 17 beta-estradiol was tested to determine its effects on the well characterized murine osteoblastic cell-line MC3T3-E1. Experiments were designed to identify the effects of estrogen on osteoblastic activities associated with both the formation and the resorption of bone. Estrogen treatment coordinately increased DNA content and alkaline phosphatase activity in MC3T3-E1 cells as much as twofold. The stimulatory effect on alkaline phosphatase was stereospecific, dose-dependent between 0.1 and ten nanomolar, and dependent on the time in culture when the hormone was administered. The effect was also persistent, since alkaline phosphatase activity remained elevated for several days after withdrawal of the hormone. Estrogen increased the levels of messenger RNA for alkaline phosphatase and type-I collagen as well, and these effects also persisted after removal of the hormone. The levels of messenger RNA for osteopontin, another bone-matrix protein, were only slightly affected by estrogen. Finally, estrogen inhibited the activation of adenylate cyclase by three osteotropic agents known to stimulate the resorption of bone: parathyroid hormone, prostaglandin E2, and the beta-adrenergic agonist isoproterenol. Thus, estrogen promoted the expression of traits associated with the formation of bone while reducing cellular responsiveness to hormones that may trigger the resorption of bone.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Direct modulation of osteoblastic activity with estrogen. 817 20

Osteopontin is a phosphorylated bone matrix sialoprotein, postulated to play a regulatory role in biomineralization. The effects of a crude preparation of rat bone osteopontin and a more highly purified bovine bone osteopontin were evaluated using a gel diffusion system to measure effects of 0.1-100 micrograms/ml of this matrix protein on hydroxyapatite formation and crystal proliferation. Bovine osteopontin at concentrations greater than 25 micrograms/ml inhibited both hydroxyapatite formation and growth in a dose-dependent manner. Osteopontin at concentrations lower than 25 micrograms/ml had no detectable effect on the amount of mineral accumulated in experiments with and without pre-formed hydroxyapatite seed crystals either when initial mineral deposition was assessed at 3.5 days, or when mineral formation and growth were assessed at 5 days. There was a statistically significant dose-dependent decrease in crystal length at all concentrations tested. The rat osteopontin preparation had similar inhibitory abilities. Partial dephosphorylation of bovine osteopontin with alkaline phosphatase removed its inhibitory ability, and reduced its ability to bind calcium. The affinity of bovine osteopontin for hydroxyapatite was determined based on a Langmuir adsorption isotherm, with values of K (binding affinity) and N (number of binding sites) being 0.026 ml/microgram and 1084 micrograms/m2, respectively. The data suggest that, in this system, osteopontin is an effective inhibitor of hydroxyapatite formation and growth due to its affinity for the hydroxyapatite crystals. In this system, osteopontin, distinct from other phosphoproteins which both promote and inhibit hydroxyapatite deposition, did not enhance mineral formation at any concentration tested.
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PMID:Osteopontin-hydroxyapatite interactions in vitro: inhibition of hydroxyapatite formation and growth in a gelatin-gel. 825 66

Differentiating chick limb-bud mesenchymal cells plated in micromass culture form a cartilage matrix that can be mineralized in the presence of 4 mM inorganic phosphate (Pi), and 1 mM calcium. Previous studies showed that when beta-glycerophosphate (beta GP) is used in place of Pi, the mineral crystals formed are larger and differ in distribution. The present study shows that the difference in distribution is not associated with alterations in cell proliferation, protein synthesis, or with collagen, proteoglycan core protein, or alkaline phosphatase gene expression. Cultures with 2.5, 5, and 10 mM beta GP did show different levels of alkaline phosphatase activity, and in the presence of low (0.3 mM) Ca had different Pi contents (4, 6 and 9 mM, respectively), indicating that the increase in CaxP product may in part be responsible for the altered pattern of mineralization. However, cultures with beta GP in which alkaline phosphatase activity was inhibited with levamisole still had an altered mineral distribution as revealed by Fourier transform-infrared (FT-IR) microspectroscopy. The presence of a casein kinase II-like activity in the mineralizing cultures, the ability of specific inhibitors of this enzyme to block mineralization, and the known ability of beta GP to block phosphoprotein phosphatase activity suggests that altered patterns of matrix protein phosphorylation may influence mineral deposition in these cultures.
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PMID:The mechanism of beta-glycerophosphate action in mineralizing chick limb-bud mesenchymal cell cultures. 891 77

The bone morphogenetic proteins (BMPs) and transforming growth factor-beta s (TGF-beta s), are a group of structurally related proteins which have been shown to stimulate bone formation in vivo. Since these proteins are concentrated in the organic matrix of bone and would be released during bone resorption, they are likely to have a profound effect on the remodeling bone and may provide a link between bone resorption and bone formation. We are using primary cultures of fetal rat calvarial cells (FRCC) to study the independent and combined effects of OP-1/BMP-7 and TGF-beta 1 on bone cells at different stages of differentiation in order to identify responding cell populations and target genes. We have confirmed prior reports that OP-1 stimulates, while TGF-beta 1 inhibits, osteogenic differentiation in this system. The increase in both number and size of the mineralized nodules induced by OP-1 was accompanied by increased expression of alkaline phosphatase and type I collagen with an induction of bone sialoprotein (BSP) suggesting that OP-1 stimulates both differentiation and clonal expansion of osteoblastic cells. Interestingly, TGF-beta 1 abrogated OP-1 induced nodule formation. Despite these opposing effects on osteogenic differentiation, TGF-beta 1 (Wrana et al, 1991) and OP-1 both stimulated a rapid induction of osteopontin (OPN) mRNA in confluent FRCC cultures enriched in pre-osteoblastic cells. In contrast, when OP-1 was added to nodule-forming cultures which are enriched in osteoblastic cells, there was only a weak induction of OPN. Moreover, while the expression of one marker for mature osteoblasts (BSP) was refractory to OP-1, another (osteocalcin) was markedly stimulated. Thus OP-1 has selective effects on bone matrix protein expression that are dependent on the differentiated state of the cells.
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PMID:Influence of osteogenic protein-1 (OP-1;BMP-7) and transforming growth factor-beta 1 on bone formation in vitro. 908 44

Estrogen (E2) has been shown to prevent bone loss among postmenopausal women. The molecular mechanism(s) by which this is accomplished is not clear. The discovery of E2 receptor (ER) in osteoblasts and osteoclasts has implicated these cells as direct targets for E2. Previous studies on the effects of E2 on osteoblastic cells in vitro or in organ culture present conflicting results, possibly due to heterogeneity in cell types, stage of differentiation, ER levels, and/or species differences. The effects of E2 on gene expression during various stages of human osteoblast cell differentiation has not been investigated extensively. In this study we employed a newly developed human fetal osteoblastic cell line (hFOB/ER9) that contains high levels of ER to examine the effects of E2 on osteoblast proliferation and differentiation. The basal levels and E2 effects on the expression of various extracellular matrix proteins were also characterized throughout different stages of differentiation. These stages include a proliferative/relatively undifferentiated stage (day 6), a matrix maturation stage (days 10-14), and a mineralization/calcified nodule stage (day 18). During the stage of rapid cell proliferation, E2 treatment of hFOB/ER9 cells resulted in a dose-dependent decrease in [3H]thymidine incorporation to a maximum of 72% compared to the vehicle control value. Treatment of hFOB/ER9 cells with 10(-9) M E2 for 48 h resulted in an increase in alkaline phosphatase (AP) activity throughout cell differentiation. The magnitude of AP induction varied from approximately 200-500%. In contrast, E2 decreased osteocalcin protein levels to a minimum of 54% compared to the vehicle control value. The steady state messenger RNA levels for AP increased and osteocalcin decreased after E2 treatment, similar to the responses observed at the protein level. At all stages, there was little or no effect of E2 on type I collagen protein levels or osteonectin steady state messenger RNA levels. The E2 responses on hFOB/ER9 cell matrix protein expression and cell proliferation were mediated through the ER, as cultures cotreated with a 100-fold molar excess of a type II anti-E2 (ICI 182,780) abrogated these effects. These results support the hypothesis that E2 does have an effect on osteoblastic differentiation by decreasing hFOB/ER9 cell proliferation and differentially regulating extracellular matrix expression.
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PMID:Estrogen regulation of human osteoblastic cell proliferation and differentiation. 920 36


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