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)

Activated platelets release a multifaceted blend of growth factors that has stimulatory effects on mesenchymal cells, both in vitro and in vivo, which imply beneficial effects on wound repair and tissue regeneration. Previous studies on fibroblast cultures have revealed that more potent growth factors, with respect to cell proliferation, are released in acidic preparations of lysed platelet concentrates in comparison with neutral and alkaline preparations. The current study was intended to investigate the influence of pH on lysed platelet concentrates with respect to release of growth factors, cell proliferation and alkaline phosphatase (ALP) activity in human osteoblast-like cells (hFOB 1.19). Cell proliferation was assessed with the MTT kit, ALP activity by conventional enzymatic reaction kinetics and growth factors platelet-derived growth factor (PDGF) and transforming growth factor-beta (TGF-beta) by enzyme-linked immunosorbent assays. Osteoblast-like cells were stimulated with lysed platelet concentrates preincubated at pH 4.4, 5.4, 7.4, and 7.6. A 3-13-fold increase of cell proliferation was found in comparison with controls and the most evident increase was observed with platelets activated at pH 5.4. The highest ALP activity was observed in preparations at pH 7.6. Platelets incubated in an acidic environment (pH 5.4) induced a higher proliferation compared with preincubation at neutral or alkaline pH and the level of PDGF was also found to be higher in acidic preincubations. The level of TGF-beta was, in contrast, lowest at pH 4.4. We suggest, based on these experimental findings, that acidic milieu influence platelets to release growth factors more potent to stimulate osteoblast proliferation than neutral and alkaline platelet preparations. Lysed platelet concentrates prepared at an alkaline pH might release additional components with stimulating effects resulting in other features than cell proliferation. This is the first report, to our knowledge, about a pH dependent stimulatory effect of lysed platelet concentrates on human osteoblast-like cell proliferation. Lysed platelet concentrates, preincubated in acidic or alkaline buffers, may benefit fracture healing, implant fixation and might also be advantageous in the treatment of wounds with platelet constituents; however, this has to be investigated in extended experimental and clinical settings.
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PMID:Variation of pH in lysed platelet concentrates influence proliferation and alkaline phosphatase activity in human osteoblast-like cells. 1736 59

We previously demonstrated that curcumin, a polyphenolic antioxidant purified from turmeric, up-regulated peroxisome proliferator-activated receptor (PPAR)-gamma gene expression and stimulated its signaling, leading to the inhibition of activation of hepatic stellate cells (HSC) in vitro. The current study evaluates the in vivo role of curcumin in protecting the liver against injury and fibrogenesis caused by carbon tetrachloride (CCl(4)) in rats and further explores the underlying mechanisms. We hypothesize that curcumin might protect the liver from CCl(4)-caused injury and fibrogenesis by attenuating oxidative stress, suppressing inflammation, and inhibiting activation of HSC. This report demonstrates that curcumin significantly protects the liver from injury by reducing the activities of serum aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase, and by improving the histological architecture of the liver. In addition, curcumin attenuates oxidative stress by increasing the content of hepatic glutathione, leading to the reduction in the level of lipid hydroperoxide. Curcumin dramatically suppresses inflammation by reducing levels of inflammatory cytokines, including interferon-gamma, tumor necrosis factor-alpha, and interleukin-6. Furthermore, curcumin inhibits HSC activation by elevating the level of PPARgamma and reducing the abundance of platelet-derived growth factor, transforming growth factor-beta, their receptors, and type I collagen. This study demonstrates that curcumin protects the rat liver from CCl(4)-caused injury and fibrogenesis by suppressing hepatic inflammation, attenuating hepatic oxidative stress and inhibiting HSC activation. These results confirm and extend our prior in vitro observations and provide novel insights into the mechanisms of curcumin in the protection of the liver. Our results suggest that curcumin might be a therapeutic antifibrotic agent for the treatment of hepatic fibrosis.
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PMID:Curcumin protects the rat liver from CCl4-caused injury and fibrogenesis by attenuating oxidative stress and suppressing inflammation. 1800 44

Activins and bone morphogenetic proteins (BMPs) are members of the transforming growth factor-beta family of growth and differentiation factors that induce signaling in target cells by assembling type II and type I receptors at the cell surface. Ligand residues involved in type II binding are located predominantly in the C-terminal region that forms an extended beta-sheet, whereas residues involved in type I binding are located in the alpha-helical and preceding loop central portion of the molecule. To test whether the central residues are sufficient to determine specificity toward type I receptors, activin A/BMP chimeras were constructed in which the central residues (45-79) of activin A were replaced with corresponding residues of BMP2 and BMP7. The chimeras were assessed for activin type II receptor (Act RII) binding, activin-like bioactivity, and BMP-like activity as well as antagonistic properties toward activin A and myostatin. ActA/BMP7 chimera retained Act RII binding affinity comparable with wild type activin A, whereas ActA/BMP2 chimera showed a slightly reduced affinity toward Act RII. Both the chimeras were devoid of significant activin bioactivity in 293T cells in the A3 Lux reporter assay up to concentrations 10-fold higher than the minimal effective activin A concentration (approximately 4 nM). In contrast, these chimeras showed BMP-like activity in a BRE-Luc assay in HepG2 cells as well as induced osteoblast-like phenotype in C2C12 cells expressing alkaline phosphatase. Furthermore, both the chimeras activated Smad1 but not Smad2 in C2C12 cells. Also, both the chimeras antagonized ligands that signal via activin type II receptor, such as activin A and myostatin. These data indicate that activin residues in the central region determine its specificity toward type I receptors. ActA/BMP chimeras can be useful in the study of receptor specificities and modulation of transforming growth factor-beta members, activins, and BMPs.
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PMID:Activin A/bone morphogenetic protein (BMP) chimeras exhibit BMP-like activity and antagonize activin and myostatin. 1805 65

Bone morphogenetic proteins (BMPs) are factors that promote osteoblastic differentiation and osteogenesis. The aim of this study was to examine the behavior of neonatal rat calvarial osteoblast cells cultured on different concentrations of BMP graft materials. Fifty thousand cells per milliliter were seeded and cultured on graft materials for 24 and 48 h. Different concentrations of BMPs (combination of BMPs numbered from 1 to 14) were supplemented to the medium. To evaluate cellular proliferation and differentiation, specimens were examined for DNA synthesis, alkaline phosphatase (ALP) activity, cell numbers, and viability of the cells. Further, transforming growth factor-beta(1) (TGF-beta(1)) and lactate dehydrogenase (LDH) levels were investigated. Morphological appearance of the specimens at 24 and 48 h of incubation was evaluated using scanning electron microcopy. Evaluations of DNA synthesis, cell count, and cell viability data revealed that a significant difference existed at 24 and 48 h (p < 0.05). The TGF-beta(1) and ALP analysis showed only a significant difference between the groups at the end of 24 h (p < 0.05). Regarding the lactate dehydrogenase activity there was not any significant difference at 24 and 48 h (p > 0.05). No morphological differences were observed in cell morphology on BMP graft material and the control group. These results indicate that BMPs have an inductive effect on osteoblast differentiation and a possible inhibitory effect in the early phases of cell proliferation.
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PMID:Effects of bone morphogenetic protein on neonatal rat calvarial osteoblast-like cells: an in vitro study. 1826 Jan 42

Osseous metaplasia within the gastrointestinal tract is a rare phenomenon, seen most frequently in mucinproducing left-sided colonic adenocarcinomas. It has also been documented in a variety of benign conditions, occurring in polyps and lesions associated with inflammation and ulceration. This is the first case report, to the authors' knowledge, of osseous metaplasia associated with a diversion proctocolitis. The diversion was performed following stricture formation, secondary to complicated diverticular disease with diverticular phlegmon formation. In common with other cases, in which osseous metaplasia arises within a background of inflammation, the present case demonstrated stromal fibroblastic proliferation. The underlying pathogenesis of osseous metaplasia has not yet been elucidated, but secretion of various bone morphogenic proteins (belonging to the transforming growth factor-beta superfamily) and increased alkaline phosphatase activity by both epithelial and stromal cells have been documented.
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PMID:Osseous metaplasia of the colon in a diversion proctocolitis. 1848 Mar 93

Human mesenchymal stem cells (hMSCs) are able to self-replicate and differentiate into a variety of cell types including osteoblasts, chondrocytes, adipocytes, endothelial cells, and muscle cells. It was reported that fibroblast growth factor-2 (FGF-2) increased the growth rate and multidifferentiation potentials of hMSCs. In this study, we investigated the genes involved in the promotion of osteogenic and chondrogenic differentiation potentials of hMSCs in the presence of FGF-2. hMSCs were maintained in the medium with FGF-2. hMSCs were harvested for the study of osteogenic or chondrogenic differentiation potential after 15 days' culture. To investigate osteogenic differentiation, the protein levels of alkaline phosphatase (ALP) and the mRNA expression levels of osteocalcin were measured after the induction of osteogenic differentiation. Moreover, the investigation for chondrogenic differentiation was performed by measuring the mRNA expression levels of type II and type X collagens after the induction of chondrogenic differentiation. The expression levels of ALP, type II collagen, and type X collagen of hMSCs cultured with FGF-2 were significantly higher than control. These results suggested that FGF-2 increased osteogenic and chondrogenic differentiation potentials of hMSCs. Furthermore, microarray analysis was performed after 15 days' culture in the medium with FGF-2. We found that the overall insulin-like growth factor-I (IGF-I) and transforming growth factor-beta (TGF-beta) signaling pathways were inactivated by FGF-2. These results suggested that the inactivation of IGF-I and TGF-beta signaling promotes osteogenic and chondrogenic differentiation potential of hMSCs in the presence of FGF-2.
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PMID:FGF-2 increases osteogenic and chondrogenic differentiation potentials of human mesenchymal stem cells by inactivation of TGF-beta signaling. 1900 35

This study evaluated the effect of TAK-778 [(2R, 4S)-(-)-N-(4-diethoxyphosphorylmethylphenyl)-1,2,4,5-tetrahydro-4-methyl-7,8-methylenedioxy-5-oxo-3-benzothiepin-2-carboxamide)] on in vitro osteogenic events and on gene expression of osteoblastic cells derived from human alveolar bone and the participation of estrogen receptors (ERs) on such effect. Osteoblastic cells were subcultured, with or without TAK-778 (10(-5) M), to evaluate cell growth and viability, total protein content, and alkaline phosphatase (ALP) activity at 7, 14, and 21 days; bone-like formation at 21 days; and gene expression, using cDNA microarray, at 7 days. Also, osteoblastic cells were exposed to TAK-778 (10(-5) M) combined to ICI182,780, a nonspecific ER antagonist (10(-6) M), and gene expression was evaluated by real-time polymerase chain reaction (PCR) at 7 days. TAK-778 induced a reduction in culture growth and an increase in cell synthesis, ALP activity, and bone-like formation. The cDNA microarray showed genes associated with cell adhesion and differentiation, skeletal development, ossification, and transforming growth factor-beta receptor signaling pathway, with a tendency to be higher expressed in cells exposed to TAK-778. The gene expression of ALP, osteocalcin, Msh homeobox 2, receptor activator of NF-kappa B ligand, and intercellular adhesion molecule 1 was increased by TAK-778 as demonstrated by real-time PCR, and this effect was antagonized by ICI182,780. The present results demonstrated that TAK-778 acts at a transcriptional level to enhance the in vitro osteogenic process and that its effect on gene expression of osteoblastic cells is mediated, at least partially, through ERs. Based on these findings, TAK-778 could be considered in the treatment of bone metabolic disorders.
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PMID:The effect of TAK-778 on gene expression of osteoblastic cells is mediated through estrogen receptor. 1906 43

The primary goal of this investigation was to develop a calcium phosphate film hybridized with 1alpha,25-dihydroxyvitamin D(3) for the improvement of osteoconductivity of bone substitutes. The hybrid films (hCaP) were prepared at the different concentrations of 1 x 10(-10), 1 x 10(-8), and 1 x 10(-6) M designated as hCaPL, hCaPM, and hCaPH, respectively. The change of the hormone concentration during the preparation of the hybrid films did not cause significant variations on the physical properties of hCaPs, i.e. surface morphology and roughness. On the other hand, X-ray photon spectroscope (XPS) measurements revealed that the concentration change affected the chemical composition of the hybrid films. Recruitment of osteoblast-like MG-63 cells was considerably improved on hCaPs compared to tissue culture plate (TCP). However, cell proliferation on hCaPs was substantially suppressed and inversely proportional to the hormone concentration used. It was observed that bone-like nodules which consisted of bead-like components and well-developed matrix were rapidly formed on hCaPs. Masson's trichrome and safranin-O stainings elucidated that the bead-like components were MG-63 cells. Safranin-O staining showed that proteoglycan was produced actively. These results indicate that the cells cultured on hCaPs were strongly stimulated by the hormone to produce proteoglycan which can be considered as an induction of premature bone formation. The number of the nodules was increased with hormone concentration and most pronounced at the hCaPH. Gene expression patterns of alkaline phosphatase (ALP), transforming growth factor-beta (TGF-beta), and osteopontin (OPN) were strongly modulated by hybridized the hormone. For ALP and OPN, gene expressions were activated earlier on hCaPs than untreated calcium phosphate (CaP) confirming the effect of the hybridization was substantial. The TGF-beta gene expression was immediately activated after seeding but difference between samples was not significant suggesting that the gene expression was modulated not by the hormone hybridization but by CaP itself. As a result, hybridization of 1,25(OH)(2)D(3) with CaP can be a potentially strong candidate to promote osteoconductivity of implant materials.
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PMID:A new method for the preparation of bioactive calcium phosphate films hybridized with 1alpha,25-dihydroxyvitamin D3. 1959 49

The aim of this study was to unravel the mechanisms by which interleukin (IL)-10, a potent pleiotropic cytokine, modulates alveolar bone homeostasis in C57BL/6 wild-type (WT) and IL-10 knockout (IL-10 KO) mice, evaluated at 8, 24, and 48 wk of age. Interleukin-10 KO mice presented significant alveolar bone loss when compared with WT mice, and this was not associated with changes in leukocyte counts or bacterial load. The levels of expression of messenger RNA (mRNA) for tumor necrosis factor-alpha (TNF-alpha), IL-1beta, IL-6, transforming growth factor-beta (TGF-beta), receptor activator of nuclear factor kappaB ligand (RANKL), osteoprotegerin (OPG), and matrix metalloproteinase 13 (MMP13) were similar between both strains, whereas a significant decrease of tissue inhibitor of metalloproteinase 1 (TIMP1) mRNA expression was found at 48 wk in IL-10 KO mice. The osteoblast markers core binding factor alpha1 (CBFA1) and type I collagen (COL-I) were expressed at similar levels in both strains, whereas the levels of alkaline phosphatase (ALP) and osteocalcin (OCN), and those of the osteocyte markers phosphate-regulating gene endopeptidases (PHEX) and dentin matrix protein 1 (DMP1) were significantly lower in IL-10 KO mice. Our results demonstrate that the alveolar bone loss in the absence of IL-10 was associated with a reduced expression of osteoblast and osteocyte markers, an effect independent of microbial, inflammatory or bone-resorptive pathways.
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PMID:Down-regulation of expression of osteoblast and osteocyte markers in periodontal tissues associated with the spontaneous alveolar bone loss of interleukin-10 knockout mice. 2015 61

Collagen glycosaminoglycan (CG) scaffolds have been clinically approved as an application for skin regeneration. The goal of this study has been to examine whether a CG scaffold is a suitable biomaterial for generating human bone tissue. Specifically, we have asked the following questions: (1) can the scaffold support human osteoblast growth and differentiation and (2) how might recombinant human transforming growth factor-beta (TGF-beta(1)) enhance long-term in vitro bone formation? We show human osteoblast attachment, infiltration and uniform distribution throughout the construct, reaching the centre within 14 days of seeding. We have identified the fully differentiated osteoblast phenotype categorised by the temporal expression of alkaline phosphatase, collagen type 1, osteonectin, bone sialo protein, biglycan and osteocalcin. Mineralised bone formation has been identified at 35 days post-seeding by using von Kossa and Alizarin S Red staining. Both gene expression and mineral staining suggest the benefit of introducing an initial high treatment of TGF-beta(1) (10 ng/ml) followed by a low continuous treatment (0.2 ng/ml) to enhance human osteogenesis on the scaffold. Osteogenesis coincides with a reduction in scaffold size and shape (up to 70% that of original). A notable finding is core degradation at the centre of the tissue-engineered construct after 49 days of culture. This is not observed at earlier time points. Therefore, a maximum of 35 days in culture is appropriate for in vitro studies of these scaffolds. We conclude that the CG scaffold shows excellent potential as a biomaterial for human bone tissue engineering.
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PMID:A novel collagen scaffold supports human osteogenesis--applications for bone tissue engineering. 2019 86


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