Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:EXPT01586 (G418)
 2,237 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human growth hormone (hGH) is frequently used clinically for growth abnormalities in children and also in adults with growth hormone deficiency. The hormone is usually administered to the individuals by frequent injections. In the present study we investigated the potential of bone marrow stromal cells as vehicles to deliver the GH in vivo by infusion of cells transduced with hGH cDNA into mice femurs. The effect of the hormone on the transduced cells in vitro was also assessed. Bone marrow stromal cells established from a mouse model of human osteogenesis imperfecta mice (oim) were transduced with a retrovirus containing hGH and neomycin resistance genes. The hGH-expressing cells were selected in a medium containing G418 and were then assessed for the hGH expression in vitro. The selected cells synthesized 15 ng/10(6) cells of hGH per 24 h in vitro and exhibited alkaline phosphatase activity when they were treated with the human recombinant bone morphogenetic protein 2 (rhBMP-2). The transduced cells also proliferated faster than the LacZ transduced cells but they did not exhibit a higher rate of matrix synthesis. When 2 x 10(6) hGH+ cells were injected into the femurs of mice, hGH was detected in the serum of the recipient mice up to 10 days after injection. The highest level of growth hormone expression, 750 pg/ml, was detected in the serum of the recipient mice I day after injection of the transduced cells. hGH was also detected in the medium conditioned by cells that were flushed from the femurs of the recipient mice at 1, 3, and 6 days after cell injection. These data indicate that bone marrow stromal cells could potentially be used therapeutically for the delivery of GH or any other therapeutic proteins targeted for bone. The data also suggest that GH may exert its effects on bone marrow stromal cells by increasing their rate of proliferation.
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PMID:In vivo expression of human growth hormone by genetically modified murine bone marrow stromal cells and its effect on the cells in vitro. 1097 31

Bone morphogenetic proteins (BMP) play a pivotal role in growth and differentiation of osteoblastic lineage cells. BMPs are potent stimulators of bone formation in various animal models. To understand the mechanism of BMP action in bone cells, we have investigated the effects of overexpression of the BMP-2 gene on proliferation and differentiation of UMR-106 rat osteosarcoma cells. A stable UMR-106 cell line overexpressing the BMP-2 gene was established by transfection of cells using a mammalian expression vector harboring human BMP-2 cDNA followed by G418 selection. After introduction of the BMP-2 gene, UMR-106 cells appeared more spindle-shaped in morphology compared to the predominantly cuboidal appearance of the parental cells. Overexpression of BMP-2 markedly inhibited proliferation as measured by cell counting and [3H]thymidine incorporation assays. Extracellular matrix (ECM) derived from cells overexpressing BMP-2 exhibited a less supportive effect on proliferation of UMR cells than did ECM derived from parental cells. Furthermore, cell-cell communication through gap junctions was reduced more than 50% as determined by nondisruptive fluorescent dye transfer assays. Overexpression of BMP-2 significantly stimulated expression of osteocalcin and alkaline phosphatase genes, indicating its role in osteoblastic differentiation. There was little effect on osteopontin gene expression.
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PMID:Overexpression of BMP-2 modulates morphology, growth, and gene expression in osteoblastic cells. 1190 Apr 83

This experiment is sought to study the contribution of different gene in osteogenous differentiation of bone marrow stromal cells (MSCs) and optimize the seed cells of bone tissue engineering. Firstly, we obtained the full length gene of BMP-2, VEGF165 and bFGF by RT-PCR, and cloned into the expression vector pcDNA3. 0. After to be transfected, the MSCs cell lines which could express each of the target protein were selected out by G418. RT-PCR and immunohistochemistry were used to confirm the exogenous gene expression in MSCs. MTT showed that almost all of the MSCs which have been transfected with exogenous gene had more strong proliferative potential than the untransfected group did. There was a notable increase of ALP activity in transfected cell compared with the control group. The concentration of OCN in cell culture medium had a increase in some degree except of VEGF group. The outstanding osteogenous differentiation could be observed in BMP-2 and bFGF transfected MSCs. The results showed that the MSCs modified by BMP-2 and bFGF would be more effective in bone tissue engineering field.
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PMID:[The study of osteogenous differentiation of MSCs transfected with different gene]. 1653 31