Full metadata record
DC Field | Value | Language |
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dc.contributor.author | 황은숙 | * |
dc.date.accessioned | 2016-08-28T12:08:56Z | - |
dc.date.available | 2016-08-28T12:08:56Z | - |
dc.date.issued | 2012 | * |
dc.identifier.issn | 0007-1188 | * |
dc.identifier.other | OAK-8470 | * |
dc.identifier.uri | https://dspace.ewha.ac.kr/handle/2015.oak/222364 | - |
dc.description.abstract | BACKGROUND AND PURPOSE The transcriptional co-activator with PDZ-binding motif (TAZ) is characterized as a transcriptional modulator of mesenchymal stem cell differentiation into osteoblasts and adipocytes. Moreover, increased TAZ activity in the nucleus enhances osteoblast differentiation and suppresses adipocyte development by interacting with runt-related transcription factor 2 (RUNX2) and PPARγ, respectively. Therefore, it would be of interest to identify low MW compounds that modulate nuclear TAZ activity. EXPERIMENTAL APPROACH High-throughput screening was performed using a library of low MW compounds in order to identify TAZ modulators that enhance nuclear TAZ localization. The effects and molecular mechanisms of a TAZ modulator have been characterized in osteoblast and adipocyte differentiation. KEY RESULTS We identified 2-butyl-5-methyl-6-(pyridine-3-yl)-3-[2′-(1H-tetrazole-5-yl)- biphenyl-4-ylmethyl]-3H-imidazo[4,5-b]pyridine] (TM-25659) as a TAZ modulator. TM-25659 enhanced nuclear TAZ localization in a dose-dependent manner and attenuated PPARγ-mediated adipocyte differentiation by facilitating PPARγ suppression activity of TAZ. In addition, TAZ-induced RUNX2 activity activation was further increased in osteoblasts, causing increased osteoblast differentiation. Accordingly, TM-25659 suppressed bone loss in vivo and decreased weight gain in an obesity model. After oral administration, TM-25659 had a favourable pharmacokinetic profile. CONCLUSION AND IMPLICATIONS TM-25659 stimulated nuclear TAZ localization and thus caused TAZ to suppress PPARγ-dependent adipogenesis and enhance RUNX2-induced osteoblast differentiation in vitro and in vivo. Our data suggest that TM-25659 could be beneficial in the control of obesity and bone loss. © 2011 The Authors. | * |
dc.language | English | * |
dc.title | TM-25659 enhances osteogenic differentiation and suppresses adipogenic differentiation by modulating the transcriptional co-activator TAZ | * |
dc.type | Article | * |
dc.relation.issue | 5 | * |
dc.relation.volume | 165 | * |
dc.relation.index | SCI | * |
dc.relation.index | SCIE | * |
dc.relation.index | SCOPUS | * |
dc.relation.startpage | 1584 | * |
dc.relation.lastpage | 1594 | * |
dc.relation.journaltitle | British Journal of Pharmacology | * |
dc.identifier.doi | 10.1111/j.1476-5381.2011.01664.x | * |
dc.identifier.wosid | WOS:000300448500031 | * |
dc.identifier.scopusid | 2-s2.0-84863134812 | * |
dc.author.google | Jang E.J. | * |
dc.author.google | Jeong H. | * |
dc.author.google | Kang J.O. | * |
dc.author.google | Kim N.J. | * |
dc.author.google | Kim M.S. | * |
dc.author.google | Choi S.H. | * |
dc.author.google | Yoo S.E. | * |
dc.author.google | Hong J.H. | * |
dc.author.google | Bae M.A. | * |
dc.author.google | Hwang E.S. | * |
dc.contributor.scopusid | 황은숙(8688011100) | * |
dc.date.modifydate | 20240123102458 | * |