https://scholars.lib.ntu.edu.tw/handle/123456789/564624
DC 欄位 | 值 | 語言 |
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dc.contributor.author | Fong Y.-C. | en_US |
dc.contributor.author | Maa M.-C. | en_US |
dc.contributor.author | Tsai F.-J. | en_US |
dc.contributor.author | Chen W.-C. | en_US |
dc.contributor.author | Lin J.-G. | en_US |
dc.contributor.author | Jeng L.-B. | en_US |
dc.contributor.author | RONG-SEN YANG | en_US |
dc.contributor.author | WEN-MEI FU | en_US |
dc.contributor.author | Tang C.-H. | en_US |
dc.date.accessioned | 2021-06-01T07:03:27Z | - |
dc.date.available | 2021-06-01T07:03:27Z | - |
dc.date.issued | 2008 | - |
dc.identifier.issn | 8840431 | - |
dc.identifier.uri | https://scholars.lib.ntu.edu.tw/handle/123456789/564624 | - |
dc.description.abstract | Introduction: The bone marrow microenvironment is further enriched by growth factors released during osteoclastic bone resorption. It has been reported that the chemokine interleukin (IL)-8 is a potent and direct activator of osteoclastic differentiation and bone resorption. However, the effect of bone-derived growth factors on the IL-8 production in human cancer cells and the promotion of osteoclastogenesis are largely unknown. The aim of this study was to investigate whether osteoblast-derived TGF-β1 is associated with osteolytic bone diseases. Materials and Methods: IL-8 mRNA levels were measured using RT-PCR analysis. MAPK phosphorylation was examined using the Western blot method. siRNA was used to inhibit the expression of TGF-β1, BMP-2, and IGF-1. DNA affinity protein-binding assay and chromatin immunoprecipitation assays were used to study in vitro and in vivo binding of c-fos, c-jun, p65, and p50 to the IL-8 promoter. A transient transfection protocol was used to examine IL-8, NF-κB, and activator protein (AP)-1 activity. Results: Osteoblast conditioned medium (OBCM) induced activation of IL-8, AP-1, and NF-κB promoter in human cancer cells. Osteoblasts were transfected with TGF-β1, BMP-2, or IGF-1 small interfering RNA, and the medium was collected after 48 h. TGF-β1 but not BMP-2 or IGF-1 siRNA inhibited OBCM-induced IL-8 release in human cancer cells. In addition, TGF-β1 also directly induced IL-8 release in human cancer cells. Activation of AP-1 and NF-κB DNA-protein binding and MAPKs after TGF-β1 treatment was shown, and TGF-β1-induced IL-8 promoter activity was inhibited by the specific inhibitors of MAPK cascades. Conclusions: In this study, we provide evidence to show that the osteoblasts release growth factors, including TGF-β1, BMP-2, and IGF-1. TGF-β1 is the major contributor to the activation of extracellular signal-related kinase (ERK), p38, and c-Jun N-terminal kinase (JNK), leading to the activation of AP-1 and NF-κB on the IL-8 promoter and initiation of IL-8 mRNA and protein release, thereby promoting osteoclastogenesis. ? 2008 American Society for Bone and Mineral Research. | - |
dc.relation.ispartof | Journal of Bone and Mineral Research | - |
dc.subject.classification | [SDGs]SDG3 | - |
dc.subject.other | bone morphogenetic protein 2; immunoglobulin enhancer binding protein; interleukin 8; messenger RNA; mitogen activated protein kinase; mitogen activated protein kinase inhibitor; mitogen activated protein kinase p38; protein c fos; protein c jun; protein p50; small interfering RNA; somatomedin C; synaptotagmin I; transcription factor AP 1; transforming growth factor beta1; immunoglobulin enhancer binding protein; interleukin 8; mitogen activated protein kinase; protein kinase inhibitor; transcription factor AP 1; article; cancer cell; cell differentiation; controlled study; cytokine production; cytokine release; enzyme activation; enzyme phosphorylation; genetic transfection; human; human cell; osteoblast; osteoclast; osteolysis; promoter region; protein DNA binding; protein secretion; reverse transcription polymerase chain reaction; Western blotting; culture medium; drug antagonism; genetics; metabolism; neoplasm; protein binding; secretion; tumor cell line; Cell Line, Tumor; Culture Media; Enzyme Activation; Humans; Interleukin-8; Mitogen-Activated Protein Kinases; Neoplasms; NF-kappa B; Osteoblasts; Promoter Regions (Genetics); Protein Binding; Protein Kinase Inhibitors; Transcription Factor AP-1; Transforming Growth Factor beta1 | - |
dc.title | Osteoblast-derived TGF-β1 stimulates IL-8 release through AP-1 and NF-κB in human cancer cells | en_US |
dc.type | journal article | en |
dc.identifier.doi | 10.1359/jbmr.080206 | - |
dc.identifier.pmid | 18435575 | - |
dc.identifier.scopus | 2-s2.0-44449166074 | - |
dc.relation.pages | 961-970 | - |
dc.relation.journalvolume | 23 | - |
dc.relation.journalissue | 6 | - |
item.openairecristype | http://purl.org/coar/resource_type/c_6501 | - |
item.openairetype | journal article | - |
item.grantfulltext | none | - |
item.cerifentitytype | Publications | - |
item.fulltext | no fulltext | - |
crisitem.author.dept | Orthopedic Surgery-NTUH | - |
crisitem.author.dept | Orthopedic Surgery | - |
crisitem.author.dept | Pharmacology | - |
crisitem.author.orcid | 0000-0002-0553-4779 | - |
crisitem.author.orcid | 0000-0003-4157-8987 | - |
crisitem.author.parentorg | National Taiwan University Hospital | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | College of Medicine | - |
顯示於: | 藥理學科所 |
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