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• W1845752854 abstract "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." @default.
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• W1845752854 date "2009-10-27" @default.
• W1845752854 modified "2023-10-15" @default.
• W1845752854 title "Aspirin induces apoptosis in mesenchymal stem cells requiring Wnt/β-catenin pathway" @default.
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• W1845752854 doi "https://doi.org/10.1111/j.1365-2184.2009.00639.x" @default.
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