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)

Chitosan is a polysaccharide scaffold used to enhance cartilage repair during treatments involving bone marrow stimulation, and it is reported to increase angiogenesis and osteogenesis in vivo. Here, we tested the hypotheses that addition of chitosan particles to the media of human bone marrow stromal cell (BMSC) cultures stimulates osteogenesis by promoting osteoblastic differentiation and by favoring the release of angiogenic factors in vitro. Confluent BMSCs were cultured for 3 weeks with 16% fetal bovine serum, ascorbate-2-phosphate and disodium beta-glycerol phosphate, in the absence or presence of dexamethasone, an anti-inflammatory glucocorticoid commonly used as an inducer of BMSC osteoblast differentiation in vitro. As expected, dexamethasone slowed cell division, stimulated alkaline phosphatase activity and enhanced matrix mineralization. Added chitosan particles accumulated intra- and extracellularly and, while not affecting most osteogenic features, they inhibited osteocalcin release to the media at day 14 and interfered with mineralized matrix deposition. Interestingly, dexamethasone promoted cell attachment and suppressed the release and activation of matrix metalloprotease-2 (MMP-2). While chitosan particles had no effect on the release of angiogenic factors, dexamethasone significantly inhibited (p<0.05 to p<0.0001) the release of vascular endothelial growth factor (VEGF), granulocyte-macrophage colony stimulating factor (GM-CSF), tumor necrosis factor-alpha (TNF-alpha), interleukins 1beta, 4, 6, and 10 (IL-1beta, IL-4, IL-6, IL-10), and a host of other inflammatory factors that were constitutively secreted by BMSCs. These results demonstrate that chitosan particles alone are not sufficient to promote osteoblast differentiation of BMSCs in vitro, and suggest that chitosan promotes osteogenesis in vivo through indirect mechanisms. Our data further show that continuous addition of dexamethasone promotes osteoblastic differentiation in vitro partly by inhibiting gelatinase activity and by suppressing inflammatory cytokines which result in increased cell attachment and cell cycle exit.
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PMID:Effect of chitosan particles and dexamethasone on human bone marrow stromal cell osteogenesis and angiogenic factor secretion. 1954 Mar 73

The purpose of this study was to determine the effects of short-term supplementation with the active compounds in green tea on serum biomarkers in patients with prostate cancer. Twenty-six men with positive prostate biopsies and scheduled for radical prostatectomy were given daily doses of Polyphenon E, which contained 800 mg of (-)-epigallocatechin-3-gallate (EGCG) and lesser amounts of (-)-epicatechin, (-)-epigallocatechin, and (-)-epicatechin-3-gallate (a total of 1.3 g of tea polyphenols), until time of radical prostatectomy. Serum was collected before initiation of the drug study and on the day of prostatectomy. Serum biomarkers hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF)-I, IGF binding protein-3 (IGFBP-3), and prostate-specific antigen (PSA) were analyzed by ELISA. Toxicity was monitored primarily through liver function enzymes. Changes in serum components were analyzed statistically using the Wilcoxon signed rank test. Cancer-associated fibroblasts were treated with EGCG, and HGF and VEGF protein and mRNA levels were measured. HGF, VEGF, PSA, IGF-I, IGFBP-3, and the IGF-I/IGFBP-3 ratio decreased significantly during the study. All of the liver function tests also decreased, five of them significantly: total protein, albumin, aspartate aminotransferase, alkaline phosphatase, and amylase. The decrease in HGF and VEGF was confirmed in prostate cancer-associated fibroblasts in vitro. Our results show a significant reduction in serum levels of PSA, HGF, and VEGF in men with prostate cancer after brief treatment with EGCG (Polyphenon E), with no elevation of liver enzymes. These findings support a potential role for Polyphenon E in the treatment or prevention of prostate cancer.
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PMID:Tea polyphenols decrease serum levels of prostate-specific antigen, hepatocyte growth factor, and vascular endothelial growth factor in prostate cancer patients and inhibit production of hepatocyte growth factor and vascular endothelial growth factor in vitro. 1954 90

The use of composite biomaterials for bone repair capitalizes on the beneficial aspects of individual materials while tailoring the mechanical properties of the composite. We hypothesized that substrate composition would modulate the osteogenic response and secretion of potent trophic factors by human mesenchymal stem cells (hMSCs). Composite scaffolds were prepared by combining nanosized hydroxyapatite (HA) and microspheres formed of poly(lactic-co-glycolic acid) (PLG) at varying ratios between 0:1 and 5:1. Scaffolds were seeded with hMSCs for culture in osteogenic conditions or subcutaneous implantation into nude rats. Compressive moduli increased with HA content in a near-linear fashion. The osteogenic differentiation of hMSCs increased in a dose-dependent manner as determined by alkaline phosphatase activity and osteopontin secretion after 4 weeks of culture. Further, endogenous secretion of vascular endothelial growth factor was sustained at significantly higher levels over 28 days for hMSCs seeded in 2.5:1 and 5:1 HA:PLG scaffolds. Eight weeks after implantation, scaffolds with higher HA:PLG ratios exhibited greater vascularization and more mineralized tissue. These data demonstrate that the mechanical properties, osteogenic differentiation, as well as the timing and duration of trophic factor secretion by hMSCs can be tailored through controlling the composition of the polymer-bioceramic composite.
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PMID:Osteogenesis and trophic factor secretion are influenced by the composition of hydroxyapatite/poly(lactide-co-glycolide) composite scaffolds. 1964 53

Plant-derived phytoestrogens have bone protective effects, but the molecular mechanism behind these effects remains unclear. This study is aimed at fully characterizing the fracture healing process of formononetin, and investigating the mechanism underlying angiogenesis in calluses of a rat fracture model. Femoral fractures were produced in 2-month-old Sprague-Dawley rats. A 20 microg/kg or 200 microg/kg dose of formononetin was orally administrated once a day during the healing period of 21 days. The results showed that in the early stage of chondrogenesis (days 3), formononetin significantly increased the number of vessels, and expression of vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR-2/flk-1) compared with control. However, the larger dose of formononetin had no significant difference on expression of VEGF and VEGFR-2/Flk-1 compared with that of the smaller dose of formononetin. After 7 days of administration, formononetin markedly induced differentiation of mesenchymal stem cells in the fracture site. After 14 days, gene expression of mesenchymal progenitors such as alkaline phosphatase (ALP), osteocalcin (OCN), osteopontin (OPN) and collagen type I (Col I), indicating osteogenic differentiation, was markedly stimulated by formononetin compared with control. These results suggest that formononetin promotes early fracture healing through angiogenesis activation in the early stage of fracture repair, and osteogenesis acceleration in the later stages, and thus may be beneficial for fracture healing.
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PMID:Formononetin promotes early fracture healing through stimulating angiogenesis by up-regulating VEGFR-2/Flk-1 in a rat fracture model. 1969 48

Parathyroid hormone-related protein (PTHrP) is an important regulator of bone remodeling. Recent studies show that this protein can induce osteogenic features through its N- and C-terminal domains. Silica-based ordered mesoporous bioceramics with an SBA-15 structure - known to be bioactive and biocompatible - have recently been evaluated for their capacity to uptake and deliver L-tryptophan. This amino acid corresponds to the end position of the 107-111 domain (called osteostatin) of the native C-terminal PTHrP (107-139) fragment, whose true action in bone metabolism is still ill-defined. In the present study, we assessed some effects of the aforementioned biomaterials pressed into disks, loaded or not with osteostatin, in osteoblastic cell cultures. Our data demonstrate that both unmodified and organically modified SBA-15 loaded with this peptide increase cell growth and the expression of several osteoblastic products (alkaline phosphatase, osteocalcin, collagen, osteoprotegerin, receptor activator of nuclear factor-kappaB ligand and vascular endothelial growth factor) in osteoblastic cells. These findings support the notion that osteostatin coating confers osteogenic features to silica-based ordered mesoporous materials, which make them suitable biomaterials for bone repair.
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PMID:Osteostatin-loaded bioceramics stimulate osteoblastic growth and differentiation. 1971 46

A number of previous studies documented the angiogenic potential of outgrowth endothelial cells in vitro and in vivo and provided evidence that therapeutic success could depend on coculture or coimplantation strategies. Thus, deeper insight into the molecular mechanisms underlying this pro-angiogenic effect of cocultures might provide new translational options for tissue engineering and regenerative medicine. One promising signaling pathway in bone repair involved in neoangiogenesis and bone formation is the sonic hedgehog (Shh) pathway. In this article, we focus on the effect of Shh on the formation of microvessel-like structures and osteoblastic differentiation in cocultures of primary osteoblasts and outgrowth endothelial cells. Already after 24 h of treatment, Shh leads to a massive increase in microvessel-like structures compared with untreated cocultures. Increased formation of angiogenic structures seems to correlate with the upregulation of vascular endothelial growth factor or angiopoietins (Ang-1 and Ang-2) studied at both the mRNA and protein levels. In addition, treatment with cyclopamine, an inhibitor of hedgehog signaling, blocked the formation of microvessel-like structures in the cocultures. However, exogenous Shh also resulted in the upregulation of several osteogenic differentiation markers in real-time polymerase chain reaction, as well as in an increased mineralization and alkaline phosphatase activity. The present data highlight the central role of the Shh pathway in bone regeneration and vascularization. Further, Shh might have the potential to improve both angiogenesis and osteogenesis in clinical applications in the future.
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PMID:Sonic hedgehog promotes angiogenesis and osteogenesis in a coculture system consisting of primary osteoblasts and outgrowth endothelial cells. 1988 47

The aim of this study was to determine how low-intensity intermittent negative pressure affects the differentiation and proliferation of human mesenchymal stem cells (MSCs), as well of OPG and OPGL mRNA expression in MSCs. MSCs were isolated from adult marrow using the density gradient separation method, passaged for three generations, and divided into the vacuum group, which was administrated at pressure of -50 kPa, for 30 min at a frequency of 2/d, and a control group. The differentiation of MSCs was examined through inverted phase contrast microscopy, measurement of alkaline phosphatase activity, alizarin-red staining, and immunohistochemistry for type I collagen, hypoxia-inducible factor-1alpha (HIF-1a), and vascular endothelial growth factor (VEGF). The MTT assay and flow cytometry were used to measure proliferation and apoptosis. Real-time PCR detected the expression of mRNA from OPG/OPGL. Compared to the control group, there was a decrease in the proliferation of cells in the vacuum group. The number of cells in S phase was reduced by 62.4%, while the rate of apoptosis, the activity of ALP, and calcium release all increased under vacuum conditions. Calcium nodes could be observed through alizarin-red staining, and the expression of collagen type I, VEGF, and HIF-1a were increased significantly. Expression of OPG mRNA was increased and the expression of OPGL mRNA decreased in the vacuum group relative to the control group. In conclusion, low-intensity intermittent negative pressure can inhibit the proliferation of human MSCs, induce differentiation to bone cells, promote the OPG mRNA expression, and reduce OPGL mRNA expression.
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PMID:Effect of negative pressure on human bone marrow mesenchymal stem cells in vitro. 2006 12

Osteoarthritis is a multifactorial disease characterized by loss of articular cartilage and subchondral plate thickening. Therefore, biochemical analysis of the underlying bone tissue has provided important information for treatment of osteoarthritis. In this study, we determined the potential role of formononetin, a phytoestrogen isolated from Astragalus membranaceus to alter the expression of metabolic markers and cytokine production of human normal osteoblasts (Obs) and osteoarthritis subchondral osteoblasts (OA Obs). Human OA Obs and normal Obs were cultured for 3days, 7days or 14days in the present medium only or were treated with various doses of formononetin. Cells were analyzed for viability by WST-8 assay, alkaline phosphatase (ALP) activity, osteogenic markers (osteocalcin (OCN) and type I collagen (Col I)) and cytokines (interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), bone morphogenic protein-2 (BMP-2)). The level of IL-6, VEGF, BMP-2, OCN and Col I was increased in OA Obs compared with normal Obs. Formononetin dose-dependently decreased ALP, IL-6, VEGF, BMP-2, OCN and Col I in OA Obs, while markedly increased ALP, VEGF, BMP-2, OCN and Col I in normal Obs. Interestingly, formononetin markedly increased the expression of VEGF and BMP-2 for 3days of culture and significantly increased OCN and Col I at 14days in human normal Obs. The remodeling effect of formononetin on osteogenic markers and cytokines of inflammatory mediators was more striking in OA Obs as well. Taken together, these results could suggest that formononetin has biphasic positive effects on normal Obs and OA Obs by modifying their biological synthetic capacities.
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PMID:Biphasic positive effect of formononetin on metabolic activity of human normal and osteoarthritic subchondral osteoblasts. 2013 55

The skeletal muscle is classified into 2 types, slow oxidative or fast glycolytic muscle. For further characterization, we investigated the capillary architecture in slow and fast muscles. The rat soleus and extensor digitorum longus (EDL) muscles were used as representatives of slow and fast muscles, respectively. To investigate capillary density, sections of both types of muscle were stained with alkaline phosphatase; the soleus muscle showed more intense reactivity, indicating that it had a denser capillary structure than the EDL muscle. We then injected fluorescent contrast medium into samples of both muscle types for light and confocal-laser microscopic evaluation. The capillary density and capillary-to-fiber ratio were significantly higher, and the course of the capillaries was more tortuous, in the soleus muscle than in the EDL muscle. Capillary coursed more tortuously in the soleus than in the EDL muscle. Succinate dehydrogenase (SDH) activity, an indicator of mitochondrial oxidative capacity, and vascular endothelial growth factor (VEGF) expression were also significantly higher in the soleus muscle. Thus, we conclude that slow oxidative muscle possess a rich capillary structure to provide demanded oxygen, and VEGF might be involved in the formation and/or maintenance of this highly capillarized architecture.
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PMID:Comparison of capillary architecture between slow and fast muscles in rats using a confocal laser scanning microscope. 2020 May 79

Skeletal defects commonly suffer from poor oxygen microenvironments resulting from compromised vascularization associated with injury or disease. Adipose stem cells (ASCs) represent a promising cell population for stimulating skeletal repair by differentiating toward the osteogenic lineage or by secreting trophic factors. However, the osteogenic or trophic response of ASCs to reduced oxygen microenvironments is poorly understood. Moreover, a direct comparison between 2D and 3D response of ASCs to hypoxia is lacking. Thus, we characterized the osteogenic and angiogenic potential of human ASCs under hypoxic (1%), normoxic (5%), and atmospheric (21%) oxygen tensions in both 2D and 3D over 4 weeks in culture. We detected greatest alkaline phosphatase activity and extracellular calcium deposition in cells cultured in both 2D and 3D under 21% oxygen, and reductions in enzyme activity corresponded to reductions in oxygen tension. ASCs cultured in 1% oxygen secreted more vascular endothelial growth factor (VEGF) over the 4-week period than cells cultured in other conditions, with cells cultured in 2D secreting VEGF in a more sustained manner than those in 3D. Expression of osteogenic markers revealed temporal changes under different oxygen conditions with peak expression occurring earlier in 3D. In addition, the increase of most osteogenic markers was significantly higher in 2D compared to 3D cultures at 1% and 5% oxygen. These results suggest that oxygen, in conjunction with dimensionality, affects the timing of the differentiation program in ASCs. These findings offer new insights for the use of ASCs in bone repair while emphasizing the importance of the culture microenvironment.
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PMID:Oxygen tension differentially influences osteogenic differentiation of human adipose stem cells in 2D and 3D cultures. 2021 46


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