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

dc.check.date2021-06-10
dc.check.infoAccess to this article is restricted until 12 months after publication by request of the publisher.en
dc.contributor.authorSartawi, Ziad
dc.contributor.authorRyan, Katie B.
dc.contributor.authorWaeber, Christian
dc.date.accessioned2020-08-10T09:05:50Z
dc.date.available2020-08-10T09:05:50Z
dc.date.issued2020-06-10
dc.date.updated2020-08-10T08:50:04Z
dc.description.abstractThe 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.description.statusPeer revieweden
dc.description.versionAccepted Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationSartawi, 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.2020.173262en
dc.identifier.doi10.1016/j.ejphar.2020.173262en
dc.identifier.endpage11en
dc.identifier.issn0014-2999
dc.identifier.journaltitleEuropean Journal of Pharmacologyen
dc.identifier.startpage1en
dc.identifier.urihttps://hdl.handle.net/10468/10371
dc.identifier.volume882en
dc.language.isoenen
dc.publisherElsevier 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.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/en
dc.subjectHUVECen
dc.subjectOsteoblastsen
dc.subjectS1P receptors 1en
dc.subjectSiponimoden
dc.subjectSphingosine 1-phosphateen
dc.titleBone regenerative potential of the selective sphingosine 1-phosphate receptor modulator siponimod: In vitro characterisation using osteoblast and endothelial cellsen
dc.typeArticle (peer-reviewed)en
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