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dc.contributor.authorDobrosak, C
dc.contributor.authorGooi, JH
dc.date.accessioned2020-12-21T04:08:32Z
dc.date.available2020-12-21T04:08:32Z
dc.date.issued2017-12
dc.identifierpii: S2352-1872(17)30031-1
dc.identifier.citationDobrosak, C. & Gooi, J. H. (2017). Increased sphingosine-1-phosphate production in response to osteocyte mechanotransduction.. Bone Rep, 7, pp.114-120. https://doi.org/10.1016/j.bonr.2017.10.002.
dc.identifier.issn2352-1872
dc.identifier.urihttp://hdl.handle.net/11343/257499
dc.description.abstractOver the past few years interest has greatly increased in how the lipid mediator sphingosine-1-phosphate (S1P) influences bone homeostasis. Recent work has postulated multiple effects of S1P on osteoblasts and osteoclasts. Based on these findings, S1P has been proposed as a potential osteoporosis treatment. However, to date, there has been only a single study investigating S1P signalling in the cells that co-ordinate bone metabolism: osteocytes. This study aimed to elucidate the role of S1P signalling in osteocyte mechanotransduction. Utilising 3D cell culture we established the expression profile of all genes related to the S1P signalling system in the Ocy454 osteocyte cell line. Exposure to mechanical loading resulted in a downregulation in Sost, Spns2, the S1P transporter, Sgpl1 and Sgppl1 the enzymes responsible for degradation and dephosphorylation of S1P. These findings, in conjunction with fluid-flow induced upregulation of Sphk1, the kinase responsible for phosphorylation of sphingosine, suggest that mechanical stimulation of osteocytes leads to an increase in intracellular S1P. This was confirmed with mechanical loading of Ocy454 cells rapidly increasing S1P production in conditioned media and protein lysates. These findings strongly suggest an important role for S1P in the response to mechanical loading of bone.
dc.languageeng
dc.publisherElsevier BV
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0
dc.titleIncreased sphingosine-1-phosphate production in response to osteocyte mechanotransduction.
dc.typeJournal Article
dc.identifier.doi10.1016/j.bonr.2017.10.002
melbourne.affiliation.departmentBiochemistry and Molecular Biology
melbourne.source.titleBone Reports
melbourne.source.volume7
melbourne.source.pages114-120
dc.rights.licenseCC BY-NC-ND
melbourne.elementsid1271182
melbourne.openaccess.pmchttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC5651498
melbourne.contributor.authorGooi, Jonathan
dc.identifier.eissn2352-1872
melbourne.accessrightsOpen Access


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