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dc.contributor.authorDeng, L.
dc.contributor.authorHu, S.
dc.contributor.authorBaydoun, A. R.
dc.contributor.authorChen, J.
dc.contributor.authorChen, X.
dc.contributor.authorCong, X.
dc.date.accessioned2013-01-11T08:59:05Z
dc.date.available2013-01-11T08:59:05Z
dc.date.issued2009
dc.identifier.citationDeng , L , Hu , S , Baydoun , A R , Chen , J , Chen , X & Cong , X 2009 , ' Aspirin induces apoptosis in mesenchymal stem cells requiring Wnt/beta-catenin pathway ' , Cell Proliferation , vol. 42 , no. 6 , pp. 721-730 . https://doi.org/10.1111/j.1365-2184.2009.00639.x
dc.identifier.issn0960-7722
dc.identifier.otherPURE: 122536
dc.identifier.otherPURE UUID: 79c19b9f-085f-4aba-9b43-4a8a46e4b2eb
dc.identifier.otherdspace: 2299/4007
dc.identifier.otherScopus: 70350464124
dc.identifier.urihttp://hdl.handle.net/2299/9557
dc.descriptionThe original article can be found at: http://www3.interscience.wiley.com Copyright Wiley Blackwell DOI: 10.1111/j.1365-2184.2009.00639.x [Full text of this article is not available in the UHRA]
dc.description.abstractBackground and Objectives: Mesenchymal stem cells (MSC) are multipotent progenitor cells that are have found use in regenerative medicine. We have previously observed that aspirin, a widely used anti-inflammatory drug, inhibits MSC proliferation. Here we have aimed to elucidate whether aspirin induces MSC apoptosis and whether this is modulated through the Wnt/β-catenin pathway. Materials and methods: Apoptosis of MSCs was assessed using Hoechst 33342 dye and an Annexin V–FITC/PI Apoptosis Kit. Expression of protein and protein phosphorylation were investigated using Western blot analysis. Caspase-3 activity was detected by applying a caspase-3/CPP32 Colorimetric Assay Kit. Results: In these MSCs, aspirin induced morphological changes characteristic of apoptosis, cytochrome c release from mitochondria, and caspase-3 activation. Stimulating the Wnt/β-catenin pathway by both Wnt 3a and GSK-3β inhibitors (LiCl and SB 216763), blocked aspirin-induced apoptosis and protected mitochondrial function, as demonstrated by decreased cytochrome c release and caspase-3 activity. Aspirin initially caused a time-dependent decrease in COX-2 expression but subsequently, and unexpectedly, elevated the latter. Stimulation of COX-2 expression by aspirin was further enhanced following stimulation of the Wnt/β-catenin pathway. Application of the COX-2 inhibitor NS-398 suppressed elevated COX-2 expression and promoted aspirin-induced apoptosis. Conclusion: These results demonstrate that the Wnt/β-catenin pathway is a key modulator of aspirin-induced apoptosis in MSCs by regulation of mitochrondrial/caspase-3 function. More importantly, our findings suggest that aspirin may influence MSC survival under certain conditions; therefore, it should be used with caution when considering regenerative MSC transplantation in patients with concomitant chronic inflammatory diseases such as arthritis.en
dc.language.isoeng
dc.relation.ispartofCell Proliferation
dc.subjectCyclin D1
dc.subjectanti-inflammatory drugs
dc.subjectcolorectal-cancer
dc.subjectsalicylic-acid
dc.titleAspirin induces apoptosis in mesenchymal stem cells requiring Wnt/beta-catenin pathwayen
dc.contributor.institutionDepartment of Human and Environmental Sciences
dc.contributor.institutionSchool of Life and Medical Sciences
dc.contributor.institutionHealth & Human Sciences Research Institute
dc.contributor.institutionPharmacology and Clinical Science Research
dc.contributor.institutionCardiovascular Pathologies
dc.contributor.institutionDiabetic neuropathies
dc.contributor.institutionBiochemistry and Bioinformatics
dc.description.statusPeer reviewed
dc.relation.schoolSchool of Life and Medical Sciences
dcterms.dateAccepted2009
rioxxterms.versionVoR
rioxxterms.versionofrecordhttps://doi.org/10.1111/j.1365-2184.2009.00639.x
rioxxterms.typeJournal Article/Review
herts.preservation.rarelyaccessedtrue


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