dc.contributor.author | Deng, L. | |
dc.contributor.author | Hu, S. | |
dc.contributor.author | Baydoun, A. R. | |
dc.contributor.author | Chen, J. | |
dc.contributor.author | Chen, X. | |
dc.contributor.author | Cong, X. | |
dc.date.accessioned | 2013-01-11T08:59:05Z | |
dc.date.available | 2013-01-11T08:59:05Z | |
dc.date.issued | 2009 | |
dc.identifier.citation | Deng , 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.issn | 0960-7722 | |
dc.identifier.other | dspace: 2299/4007 | |
dc.identifier.uri | http://hdl.handle.net/2299/9557 | |
dc.description | The 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.abstract | Background 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.format.extent | 830253 | |
dc.language.iso | eng | |
dc.relation.ispartof | Cell Proliferation | |
dc.subject | Cyclin D1 | |
dc.subject | anti-inflammatory drugs | |
dc.subject | colorectal-cancer | |
dc.subject | salicylic-acid | |
dc.title | Aspirin induces apoptosis in mesenchymal stem cells requiring Wnt/beta-catenin pathway | en |
dc.contributor.institution | Department of Human and Environmental Sciences | |
dc.contributor.institution | School of Life and Medical Sciences | |
dc.contributor.institution | Health & Human Sciences Research Institute | |
dc.contributor.institution | Pharmacology and Clinical Science Research | |
dc.contributor.institution | Cardiovascular Pathologies | |
dc.contributor.institution | Diabetic neuropathies | |
dc.contributor.institution | Biochemistry and Bioinformatics | |
dc.description.status | Peer reviewed | |
rioxxterms.versionofrecord | 10.1111/j.1365-2184.2009.00639.x | |
rioxxterms.type | Journal Article/Review | |
herts.preservation.rarelyaccessed | true | |