Bone regenerative potential of the selective sphingosine 1-phosphate receptor modulator siponimod: In vitro characterisation using osteoblast and endothelial cells

Show simple item record

dc.contributor.author Sartawi, Ziad
dc.contributor.author Ryan, Katie B.
dc.contributor.author Waeber, Christian
dc.date.accessioned 2020-08-10T09:05:50Z
dc.date.available 2020-08-10T09:05:50Z
dc.date.issued 2020-06-10
dc.identifier.citation Sartawi, Z., Ryan, K. B. and Waeber, C. (2020) 'Bone regenerative potential of the selective sphingosine 1-phosphate receptor modulator siponimod: In vitro characterisation using osteoblast and endothelial cells', European Journal of Pharmacology, 882, 173262 (11pp). doi: 10.1016/j.ejphar.2020.173262 en
dc.identifier.volume 882 en
dc.identifier.startpage 1 en
dc.identifier.endpage 11 en
dc.identifier.issn 0014-2999
dc.identifier.uri http://hdl.handle.net/10468/10371
dc.identifier.doi 10.1016/j.ejphar.2020.173262 en
dc.description.abstract The repair of critical bone defects remains a significant therapeutic challenge. While the implantation of drug-eluting scaffolds is an option, a drug with the optimal pharmacological properties has not yet been identified. Agents acting at sphingosine 1-phosphate (S1P) receptors have been considered, but those investigated so far do not discriminate between the five known S1P receptors. This work was undertaken to investigate the potential of the specific S1P1/5 modulator siponimod as a bone regenerative agent, by testing in vitro its effect on cell types critical to the bone regeneration process. hFOB osteoblasts and HUVEC endothelial cells were treated with siponimod and other S1P receptor modulators and investigated for changes in intracellular cyclic AMP content, viability, proliferation, differentiation, attachment and cellular motility. Siponimod showed no effect on the viability and proliferation of osteoblasts and endothelial cells, but increased osteoblast differentiation (as shown by increased alkaline phosphatase activity). Furthermore, siponimod significantly increased endothelial cell motility in scratch and transwell migration assays. These effects on osteoblast differentiation and endothelial cell migration suggest that siponimod may be a potential agent for the stimulation of localised differentiation of osteoblasts in critical bone defects. en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher Elsevier B.V. en
dc.rights © 2020, Elsevier B.V. All rights reserved. This manuscript version is made available under the CC BY-NC-ND 4.0 license. en
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/ en
dc.subject HUVEC en
dc.subject Osteoblasts en
dc.subject S1P receptors 1 en
dc.subject Siponimod en
dc.subject Sphingosine 1-phosphate en
dc.title Bone regenerative potential of the selective sphingosine 1-phosphate receptor modulator siponimod: In vitro characterisation using osteoblast and endothelial cells en
dc.type Article (peer-reviewed) en
dc.internal.authorcontactother Christian Waeber, School Of Pharmacy, University College Cork, Cork, Ireland. +353-21-490-3000 Email: c.waeber@ucc.ie en
dc.internal.availability Full text available en
dc.check.info Access to this article is restricted until 12 months after publication by request of the publisher. en
dc.check.date 2021-06-10
dc.date.updated 2020-08-10T08:50:04Z
dc.description.version Accepted Version en
dc.internal.rssid 522594688
dc.description.status Peer reviewed en
dc.identifier.journaltitle European Journal of Pharmacology en
dc.internal.copyrightchecked Yes
dc.internal.licenseacceptance Yes en
dc.internal.IRISemailaddress c.waeber@ucc.ie en
dc.internal.bibliocheck 173262 en


Files in this item

This item appears in the following Collection(s)

Show simple item record

© 2020, Elsevier B.V. All rights reserved. This manuscript version is made available under the CC BY-NC-ND 4.0 license. Except where otherwise noted, this item's license is described as © 2020, Elsevier B.V. All rights reserved. This manuscript version is made available under the CC BY-NC-ND 4.0 license.
This website uses cookies. By using this website, you consent to the use of cookies in accordance with the UCC Privacy and Cookies Statement. For more information about cookies and how you can disable them, visit our Privacy and Cookies statement