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)

We proposed a novel combined gene therapy of human vascular endothelial growth factor 165 gene (hVEGF165) and human bone morphogenetic protein 2 gene (hBMP2) for bone regeneration by lentivirus-mediated co-transfection of both genes into rat bone marrow-derived mesenchymal stromal cells (MSCs). Both genes were successfully co-expressed in MSCs confirmed by real-time PCR and ELISA. And the alkaline phosphatase activity of MSCs was significantly augmented by the co-transfection with both genes than any single gene transfection (P < 0.01). These results demonstrated the feasibility of the combined gene therapy by using MSCs lentivirally co-transfected with hVEGF165 and hBMP2 for bone regeneration.
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PMID:Osteogenic differentiation effects on rat bone marrow-derived mesenchymal stromal cells by lentivirus-mediated co-transfection of human BMP2 gene and VEGF165 gene. 1789 80

Zoledronic acid (ZOL) has been shown to reduce osteolysis in bone metastasis. Its efficacy in osteosarcoma has not been convincingly proved in a clinically relevant model for the disease. In vitro, ZOL decreased osteosarcoma cell proliferation, mainly due to an increase in apoptosis in a dose-dependent fashion. There was a decrease in cell migration at >or=10 micromol/L concentrations, but invasion was inhibited at a much lower dose of 0.1 micromol/L. Reverse transcription-PCR showed that ZOL overall caused an increased expression of osteocalcin and decreased expression of alkaline phosphatase, osteopontin, osteonectin, and vascular endothelial growth factor, with no change in expression of osteoprotegerin. ZOL administration s.c. twice weekly at 0.12 mg/kg to SaOS-2 tumor-bearing mice resulted in primary tumor growth inhibition, reduction in lung metastases, and dramatic decrease in osteolysis. Furthermore, in the ZOL cohort, there was a clear reduction in the number of osteoclasts in bone exposed to tumor and a lower tumor vessel density. These data point to the adjuvant potential of ZOL in the management of osteosarcoma not only for its antiosteolytic properties but also for its ability to directly halt tumor cell growth and metastasis via its effects on viability, invasion, differentiation, and angiogenesis.
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PMID:Zoledronic acid inhibits osteosarcoma growth in an orthotopic model. 1808 20

The purpose of this study was to examine the expression of vascular endothelial growth factor (VEGF) during osteoblastic differentiation of cultured human periosteal-derived cells. Periosteal tissues were obtained from mandible during surgical extraction of lower impacted third molars. Periosteal-derived cells were introduced into cell culture. After passage 3, the periosteal-derived cells were further cultured for 42 days in an osteogenic-inductive culture medium containing dexamethasone, ascorbic acid, and beta-glycerophosphate. The alkaline phosphatase activity in the cultured periosteal-derived cells increased rapidly up to day 14, followed by decrease in activity. The Runx2 protein was expressed at day 7 and day 14, and its expression was not observed thereafter. Both VEGF(165) and VEGF(121) were expressed strongly at days 35 and 42 of culture, particularly during the later stages of differentiation. Alizarin red S-positive nodules were first observed on day 14 and then increased in number during the entire culture period. Osteocalcin and VEGF were first detected in the culture medium on day 14, and their levels increased thereafter in a time-dependent manner. These results suggest that VEGF secretion from cultured human periosteal-derived cells increases along with the mineralization process of the extracellular matrix.
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PMID:Vascular endothelial growth factor expression in cultured periosteal-derived cells. 1829 84

Macrophages play a pivotal role in the development of newly formed vascular networks, in addition to their normal immunological functions. This research focuses on peritoneal macrophages as a novel source in cell implantation therapy for ischemic diseases. In this study, production of angiogenic growth factors by peritoneal macrophages and its in vivo effect of neovascularization were evaluated. Mononuclear cells from the peritoneal cavity (P-MNCs) enriched with macrophages were isolated and stimulated with hypoxia and interleukin-1beta (IL-1beta) to mimic an ischemic tissue environment in vitro. Expression of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) of mRNA in P-MNCs was apparently enhanced by hypoxic stimulation, and the production of VEGF protein was also augmented by hypoxia and IL-1beta. A rat ischemic hind limb model was created and P-MNCs (8 x 10(6)/limb) were injected into the ischemic muscles. The blood flow, which was assessed using the colored microsphere method, showed that the percentage blood flow was significantly increased by P-MNCs injection 4 weeks after surgery (48.3 +/- 16.8% in noninjected ischemic limb vs. 84.3 +/- 13.0% in the P-MNCs-injected limb). A histological analysis revealed that the number of capillaries detected by alkaline phosphatase staining was increased in the P-MNCs group 4 weeks after injection. Furthermore, the number of alpha-smooth muscle actin-positive vessels also showed a significant increase following P-MNC injection. The injected P-MNCs labeled with fluorescence were detected in the interstitial space of ischemic muscles, and VEGF protein expression of the implanted cells was confirmed by immunohistochemistry. These results indicate that peritoneal macrophages stimulate capillary formation and arteriogenesis in the ischemic limbs, possibly through the production of angiogenic growth factors. These findings suggest that the physiological angiogenic property of peritoneal macrophages could therefore be utilized for neovascularization in cell implantation therapy.
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PMID:The local injection of peritoneal macrophages induces neovascularization in rat ischemic hind limb muscles. 1846 52

The identification of suitable stem cell cultures and differentiating conditions that are free of xenogenic growth supplements is an important step in finding the clinical applicability of cell therapy in two important fields of human medicine: heart failure and bone remodeling, growth and repair. We recently demonstrated the possibility of obtaining cardiac stem cells (CSCs) from human endomyocardial biopsy specimens. CSCs self-assemble into multi-cellular clusters known as cardiospheres (CSps) that engraft and partially regenerate infarcted myocardium. CSps and cardiosphere-derived-cells (CDCs) were exposed for five days in an incubator regulated for temperature, humidity, and CO(2) inside a solenoid system. This system was placed in a magnetically shielded room. The cells were exposed simultaneously to a static magnetic field (MF) and a parallel low-alternating frequency MF, close to the cyclotron frequency corresponding to the charge/mass ratio of the Ca(++) ion. In this exposure condition, CSps and CDCs modulate their differentiation turning on cardiogenesis and turning off vasculogenesis. Cardiac markers such as troponin I (TnI) and myosin heavy chain (MHC) were up-regulated. Conversely, angiogenic markers such as vascular endothelial growth factor (VEGF) and kinase domain receptor (KDR) were down-regulated as evidenced by immunocytochemistry. Exposure to the 7 Hz calcium ion cyclotron resonance (ICR) frequency can modulate the cardiogenic vs. angiogenic differentiation process of ex vivo expanded CSCs. This may pave the way for novel approaches in tissue engineering and cell therapy. With regard to bone remodeling, it has been suggested that bone marrow-derived mesenchymal stem cells (MSC) may be considered as a potential therapeutic tool. Using the Ca(++)-dependent specific differentiation potential of the ELF-MF 7 Hz ICR, we show here that exposure of human MSC to these same MF conditions enhanced the expression of osteoblast differentiation markers such as alkaline phosphatase, osteocalcin, and osteopontin, as analyzed by real-time quantitative PCR, without affecting cell proliferation. As expected, while the differentiation marker factors were up regulated, the ICR electromagnetic field down regulated osteoprotegerin gene expression, a critical regulator of postnatal skeletal development and homeostasis in humans as well as mice.
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PMID:Ion cyclotron resonance as a tool in regenerative medicine. 1856 30

Angiogenesis plays a key role in tumour growth and metastasis. The teleost zebrafish (Danio rerio) represents a promising alternative model in cancer research. Here, we describe a zebrafish yolk membrane (ZFYM) angiogenesis assays based on the injection of 1-30 ng of human recombinant FGF2 (rFGF2) in the perivitelline space of zebrafish embryos in the proximity of developing subintestinal vein vessels (SIVs) at 48 hrs after fertilization. The rFGF2 induces a rapid and dose-dependent angiogenic response from the SIV basket, characterized by the ectopic growth of newly formed, alkaline phosphatase-positive blood vessels. These vessels are formed by proliferating cells that incorporate bromodeoxyuridine and express the endothelial cell markers vegfr2/kdr and fli1. Microangiography shows that rFGF2-induced vessels are patent and connected to the systemic circulation of the embryo. In keeping with these observations, fli1:EGFP(+) cells isolated from transgenic tg(fli1:EGFP)(y1) zebrafish embryos express the tyrosine kinase (TK) FGF receptor-1 (FGFR1) and activate extracellular signal-regulated kinase signalling when stimulated in vitro by rFGF2. The low molecular weight TK-FGFR1 inhibitor SU5402 and the high molecular weight FGF2 antagonist long-pentraxin 3 inhibit the angiogenic activity of rFGF2 when added to fish water or when co-injected with the growth factor, respectively. Moreover, similar to rFGF2, injection of the zebrafish form of vascular endothelial growth factor-A (VEGF-A) induces a significant angiogenic response in the ZFYM assay that is suppressed by the VEGF receptor-2/KDR TK inhibitor SU5416. The ZFYM assay represents a novel tool for testing the activity of low and high molecular weight inhibitors targeting a defined angiogenic growth factor in zebrafish. The assay may offer significant advantages when compared to other animal models.
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PMID:Fibroblast growth factor 2-induced angiogenesis in zebrafish: the zebrafish yolk membrane (ZFYM) angiogenesis assay. 1865 28

The aim of this study was to investigate the behavior of rat periodontal ligament (PDL) cells cultured on fibroblast growth factor-2 (FGF-2)-immobilized titanium surfaces treated by oxygen (O2) plasma. We used cell disks (15 mm in diameter), and 35-mm culture dishes sputter-coated with titanium. These were treated with oxygen plasma and dipped in FGF-2 solution. Immobilized FGF-2 was visualized with a confocal laser-scanning microscope, and its weight was calculated to be approximately 22.6 ng/cm(2) using a quartz crystal microbalance-dissipation apparatus. The PDL cells were obtained from rat incisors. Cells from fourth subculture were seeded onto the FGF-2-immobilized titanium surface. Proliferation ratio, alkaline phosphatase (ALP) activity, and expressions of type I collagen and vascular endothelial growth factor (VEGF) mRNAs were evaluated. Proliferation ratio and expressions of type I collagen and VEGF mRNAs were significantly higher, whereas ALP activity was significantly lower in FGF-2-immobilized cells than in control group (p < 0.05). These findings suggest that oxygen plasma modification can immobilize FGF-2 onto a titanium surface. Immobilized FGF-2, although inferior to culture medium with FGF-2, influenced the proliferation of PDL cells and might have promoted collagen and vascular synthesis.
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PMID:Behavior of rat periodontal ligament cells on fibroblast growth factor-2-immobilized titanium surfaces treated by plasma modification. 1876 59

Breast carcinomas show a trend toward bone metastasis that is prevalent worldwide. Celecoxib (CX) and minocycline hydrochloride (MH) have both been widely used in treating breast cancer; however, their combined effects on the osseous metastasis of breast cancer have not yet been studied. In the present study, breast cancer cells were injected into the back of the femoral bone of nude mice, and CX and MH were intraperitoneally administered every other day at doses of 30 and 40 mg/kg/day, respectively, for 30 days. Tumor weights and volumes were significantly lower and the tumor inhibition rate was significantly higher in the CX + MH group than those of the control and CX or MH alone groups (p < 0.05). The cell density in the tumor tissue was significantly decreased and apoptotic and necrotic cell death was significantly increased in the CX + MH group, as compared with those of the control and CX or MH alone groups. Microvessel density and expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinase (MMP)-9 in the tumor tissues of the CX + MH group were significantly lower than those of the CX, MH, and control groups. The serum alkaline phosphatase level of the CX + MH group was significantly lower than those of the other groups (p < 0.01). These results suggest that a combined use of CX and MH has better inhibitory effects on the osseous metastasis of breast cancer, as compared to CX or MH alone. They exerted their combined effects by increasing tumor-cell death and decreasing the tumor expression of MMP-9 and VEGF systems.
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PMID:The combined effects of celecoxib and minocycline hydrochloride on inhibiting the osseous metastasis of breast cancer in nude mice. 1877 51

Periosteum has been demonstrated to contain mesenchymal progenitor cells differentiating to osteoblasts, and both bone morphogenetic protein-2 (BMP-2) and vascular endothelial growth factor (VEGF) may play important roles in cell-based approaches to bone regeneration. The purpose of this study was to evaluate the feasibility and efficacy of BMP-2 and/or VEGF on periosteal cell differentiation to osteoblasts in vitro and ectopic bone formation in vivo. Human periosteum-derived cells were transfected with BMP-2, VEGF, BMP-2 + VEGF, or vehicle as a control by non-viral gene transfer and then cultured and implanted to nude mice intramuscularly. Real-time polymerase chain reaction analysis of the culture revealed that transgenes for BMP-2 and BMP-2 + VEGF induced more mRNA expression of alkaline phosphatase, collagen type I, and osteocalcin than VEGF and vehicle treatments; additionally, alizarin red S staining, alkaline phosphatase staining, and alkaline phosphatase activity were significantly higher in the BMP-2 + VEGF transgene than in the other versions. After implantation, ectopic bone was observed at 4 weeks and greatly increased at 8 weeks in all groups. In particular, the combination of BMP-2 and VEGF formed significantly more bone at 4 weeks, and VEGF transfection resulted in more blood vessels relative to the conditions without VEGF. Thus, VEGF might enhance BMP2-induced bone formation through modulation of angiogenesis.
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PMID:Bone morphogenetic protein-2 (BMP-2) and vascular endothelial growth factor (VEGF) transfection to human periosteal cells enhances osteoblast differentiation and bone formation. 1877 14

Electrical stimulation (ES) can activate diverse biostimulatory responses in a range of tissues. Of various forms of ES, the application of biphasic electric current (BEC) is a new approach to bone formation. This study is to investigate the effects and mechanism of action of BEC in osteoblast differentiation and cytokine production in human mesenchymal stromal cells (hMSCs). Using an in vitro culture system with a modified version of the BEC stimulator chip used in our previous study, we exposed hMSCs to a 100 Hz ES with a magnitude of 1.5/15 muA/cm(2) for 250/25 mus. hMSCs showed increased proliferation during static BEC stimulation for 5 days. However, alkaline phosphatase activity and calcium deposition were enhanced in hMSCs 7 days after the stimulation, rather than during the period of ES. BEC induced vascular endothelial growth factor (VEGF) and BMP-2 production; the former can enhance the proliferation of human umbilical vein endothelial cells in culture using conditioned media from BEC cultures. Treatment with selective inhibitors of p38 MAPK (SB203580) or Erk (PD98059), as well as calcium channel blockers (verapamil and nifedipine), reduced the BEC-mediated increase of VEGF expression and cell proliferation. These findings reveal that BEC is involved in the osteoblast differentiation of hMSCs through enhancement of cell proliferation and modulation of the local endocrine environment through VEGF and BMP-2 induction through the activation of MAPK (Erk and p38) and the calcium channel. Thus, local stimulation using BEC might be most beneficial in promoting osteogenic differentiation of hMSCs, resulting in enhanced bone formation for bone tissue engineering.
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PMID:Novel effect of biphasic electric current on in vitro osteogenesis and cytokine production in human mesenchymal stromal cells. 1929 69


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