File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Development of a High-Throughput Screening Strategy for Upregulators of the OPG/RANKL Ratio with the Potential for Antiosteoporosis Effects

TitleDevelopment of a High-Throughput Screening Strategy for Upregulators of the OPG/RANKL Ratio with the Potential for Antiosteoporosis Effects
Authors
Keywordshigh-throughput screening (HTS)
osteoporosis
osteoprotegerin (OPG)
receptor activator of NF--κB ligand (RANKL)
Issue Date2019
PublisherSage Science Press (US). The Journal's web site is located at http://www.sagepub.com/journal.aspx?pid=9162
Citation
Journal of Biomolecular Screening, , v. 21 n. 7, p. 738-748 How to Cite?
AbstractThe ratio between osteoprotegerin (OPG) and the receptor activator of NF-κB ligand (RANKL) in the bone microenvironment indicates the level of osteoclastogenesis, and upregulation of this ratio would improve osteoporosis. In this study, we established a novel high-throughput screening (HTS) system using two stably transfected monoclonal cell lines that either express firefly luciferase under the OPG promoter control or concurrently express firefly and renilla luciferases under control of the OPG and RANKL promoters, respectively. With this system, we can conveniently and rapidly detect the effects of compounds on the expression of OPG and RANKL through changes in firefly and renilla luciferase activities. A total of 8160 compounds were screened using this system, yielding five compounds without previously reported activity. The compound with greatest potential is E05657 with high activity and low effective concentration in the HTS system. It increases the OPG/RANKL ratio and OPG secretion, decreases the NFATc1 expression, and reduces osteoclastogenesis in vitro. These results indicate that this novel HTS system can be used to identify small molecules with potential antiosteoporosis effects, and E05657 is a promising lead compound as a novel antiosteoporosis drug. © Society for Laboratory Automation and Screening.
Persistent Identifierhttp://hdl.handle.net/10722/275140
ISSN
2018 Impact Factor: 2.297
2015 SCImago Journal Rankings: 1.122
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorGong, S-
dc.contributor.authorHan, X-
dc.contributor.authorLi, X-
dc.contributor.authorYang, J-
dc.contributor.authorHe, X-
dc.contributor.authorSi, S-
dc.date.accessioned2019-09-10T02:36:20Z-
dc.date.available2019-09-10T02:36:20Z-
dc.date.issued2019-
dc.identifier.citationJournal of Biomolecular Screening, , v. 21 n. 7, p. 738-748-
dc.identifier.issn1087-0571-
dc.identifier.urihttp://hdl.handle.net/10722/275140-
dc.description.abstractThe ratio between osteoprotegerin (OPG) and the receptor activator of NF-κB ligand (RANKL) in the bone microenvironment indicates the level of osteoclastogenesis, and upregulation of this ratio would improve osteoporosis. In this study, we established a novel high-throughput screening (HTS) system using two stably transfected monoclonal cell lines that either express firefly luciferase under the OPG promoter control or concurrently express firefly and renilla luciferases under control of the OPG and RANKL promoters, respectively. With this system, we can conveniently and rapidly detect the effects of compounds on the expression of OPG and RANKL through changes in firefly and renilla luciferase activities. A total of 8160 compounds were screened using this system, yielding five compounds without previously reported activity. The compound with greatest potential is E05657 with high activity and low effective concentration in the HTS system. It increases the OPG/RANKL ratio and OPG secretion, decreases the NFATc1 expression, and reduces osteoclastogenesis in vitro. These results indicate that this novel HTS system can be used to identify small molecules with potential antiosteoporosis effects, and E05657 is a promising lead compound as a novel antiosteoporosis drug. © Society for Laboratory Automation and Screening.-
dc.languageeng-
dc.publisherSage Science Press (US). The Journal's web site is located at http://www.sagepub.com/journal.aspx?pid=9162-
dc.relation.ispartofJournal of Biomolecular Screening-
dc.rightsJournal of Biomolecular Screening. Copyright © Sage Science Press (US).-
dc.subjecthigh-throughput screening (HTS)-
dc.subjectosteoporosis-
dc.subjectosteoprotegerin (OPG)-
dc.subjectreceptor activator of NF--κB ligand (RANKL)-
dc.titleDevelopment of a High-Throughput Screening Strategy for Upregulators of the OPG/RANKL Ratio with the Potential for Antiosteoporosis Effects-
dc.typeArticle-
dc.identifier.emailLi, X: sxueli@hku.hk-
dc.identifier.authorityLi, X=rp02531-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1177/1087057116654657-
dc.identifier.pmid27301430-
dc.identifier.scopuseid_2-s2.0-84979224188-
dc.identifier.hkuros303159-
dc.identifier.volume21-
dc.identifier.issue7-
dc.identifier.spage738-
dc.identifier.epage748-
dc.identifier.isiWOS:000381003500010-
dc.publisher.placeUnited States-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats