Full metadata record
DC Field | Value | Language |
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dc.contributor.author | Park, Hyun-Jung | - |
dc.contributor.author | Baek, Kyunghwa | - |
dc.contributor.author | Baek, Jeong-Hwa | - |
dc.contributor.author | Kim, Hyung-Ryong | - |
dc.date.available | 2017-08-10T08:16:40Z | - |
dc.date.created | 2017-08-09 | - |
dc.date.issued | 2017-03 | - |
dc.identifier.issn | 1661-6596 | - |
dc.identifier.uri | http://hdl.handle.net/20.500.11750/4227 | - |
dc.description.abstract | Tumor necrosis factor α (TNFα) is known to upregulate the expression of receptor activator of NF-κB ligand (RANKL). We investigated the role of the calcineurin/nuclear factor of activated T-cells (NFAT) signaling pathway in TNFα-induced RANKL expression in C2C12 and primary cultured mouse calvarial cells. TNFα-induced RANKL expression was blocked by the calcineurin/NFAT pathway inhibitors. TNFα increased NFAT transcriptional activity and subsequent RANKL promoter binding. Mutations in the NFAT-binding element (MT(N)) suppressed TNFα-induced RANKL promoter activity. TNFα increased prostaglandin E2 (PGE2) production, which in turn enhanced NFAT transcriptional activity and binding to the RANKL promoter. MT(N) suppressed PGE2-induced RANKL promoter activity. TNFα and PGE2 increased the expression of RANKL, NFAT cytoplasmic-1 (NFATc1), cAMP response element-binding protein (CREB), and cyclooxygenase 2 (COX2); which increment was suppressed by indomethacin, a COX inhibitor. Mutations in the CRE-like element blocked PGE2-induced RANKL promoter activity. PGE2 induced the binding of CREB to the RANKL promoter, whereas TNFα increased the binding of both CREB and NFATc1 to this promoter through a process blocked by indomethacin. The PGE2 receptor antagonists AH6809 and AH23848 blocked TNFα-induced expression of RANKL, NFATc1, and CREB; transcriptional activity of NFAT; and binding of NFATc1 or CREB to the RANKL promoter. These results suggest that TNFα-induced RANKL expression depends on PGE2 production and subsequent transcriptional activation/enhanced binding of NFATc1 and CREB to the RANKL promoter. © 2017 by the authors. Licensee MDPI, Basel, Switzerland. | - |
dc.language | English | - |
dc.publisher | Multidisciplinary Digital Publishing Institute (MDPI) | - |
dc.title | TNF alpha Increases RANKL Expression via PGE(2)-Induced Activation of NFATc1 | - |
dc.type | Article | - |
dc.identifier.doi | 10.3390/ijms18030495 | - |
dc.identifier.scopusid | 2-s2.0-85014071969 | - |
dc.identifier.bibliographicCitation | International Journal of Molecular Sciences, v.18, no.3 | - |
dc.description.isOpenAccess | TRUE | - |
dc.subject.keywordAuthor | TNF alpha | - |
dc.subject.keywordAuthor | RANKL | - |
dc.subject.keywordAuthor | PGE(2) | - |
dc.subject.keywordAuthor | NFATc1 | - |
dc.subject.keywordAuthor | CREB | - |
dc.subject.keywordPlus | Gene Expression Regulation | - |
dc.subject.keywordPlus | 6 Isopropoxy 9 Oxoxanthene 2 Carboxylic Acid | - |
dc.subject.keywordPlus | 7 [5 (4 Biphenylylmethoxy) 2 Morpholino 3 Oxocyclopentyl] 4 Heptenoic Acid | - |
dc.subject.keywordPlus | Animal | - |
dc.subject.keywordPlus | Animals | - |
dc.subject.keywordPlus | Biphenyl Compounds | - |
dc.subject.keywordPlus | Biphenyl Derivative | - |
dc.subject.keywordPlus | Bone Resorption | - |
dc.subject.keywordPlus | Calcineurin | - |
dc.subject.keywordPlus | Cell Line | - |
dc.subject.keywordPlus | CREB | - |
dc.subject.keywordPlus | Cyclic AMP Response Element Binding Protein | - |
dc.subject.keywordPlus | Cyclic AMP Responsive Element Binding Protein | - |
dc.subject.keywordPlus | Cyclooxygenase 2 | - |
dc.subject.keywordPlus | Dinoprostone | - |
dc.subject.keywordPlus | DNA Responsive Element | - |
dc.subject.keywordPlus | Drug Effects | - |
dc.subject.keywordPlus | Gene Expression | - |
dc.subject.keywordPlus | High Extracellular Calcium | - |
dc.subject.keywordPlus | Metabolism | - |
dc.subject.keywordPlus | Mice | - |
dc.subject.keywordPlus | Mouse | - |
dc.subject.keywordPlus | Necrosis Factor Alpha | - |
dc.subject.keywordPlus | NF Kappa B | - |
dc.subject.keywordPlus | Genetics | - |
dc.subject.keywordPlus | NFATC Transcription Factors | - |
dc.subject.keywordPlus | NFATc1 | - |
dc.subject.keywordPlus | Osteoclast Differentiation Factor | - |
dc.subject.keywordPlus | Osteoclastogenesis In Vitro | - |
dc.subject.keywordPlus | Xanthones | - |
dc.subject.keywordPlus | PGE2 | - |
dc.subject.keywordPlus | Promoter Region | - |
dc.subject.keywordPlus | Promoter Regions, Genetic | - |
dc.subject.keywordPlus | Prostaglandin E2 | - |
dc.subject.keywordPlus | Prostanoid Receptors | - |
dc.subject.keywordPlus | Protein Binding | - |
dc.subject.keywordPlus | RANK Ligand | - |
dc.subject.keywordPlus | RANKL | - |
dc.subject.keywordPlus | Receptor Activator | - |
dc.subject.keywordPlus | Response Elements | - |
dc.subject.keywordPlus | Rheumatoid Arthritis | - |
dc.subject.keywordPlus | Signal Transduction | - |
dc.subject.keywordPlus | Synovial Fibroblasts | - |
dc.subject.keywordPlus | TNF Alpha | - |
dc.subject.keywordPlus | Transcription Factor NFAT | - |
dc.subject.keywordPlus | Tumor Necrosis Factor | - |
dc.subject.keywordPlus | Tumor Necrosis Factor Alpha | - |
dc.subject.keywordPlus | Xanthone Derivative | - |
dc.citation.number | 3 | - |
dc.citation.title | International Journal of Molecular Sciences | - |
dc.citation.volume | 18 | - |