Aspirin induces apoptosis in mesenchymal stem cells requiring Wnt/β-catenin pathway
Version of Record online: 25 AUG 2009
© 2009 The Authors. Journal compilation © 2009 Blackwell Publishing Ltd
Volume 42, Issue 6, pages 721–730, December 2009
How to Cite
Deng, L., Hu, S., Baydoun, A. R., Chen, J., Chen, X. and Cong, X. (2009), Aspirin induces apoptosis in mesenchymal stem cells requiring Wnt/β-catenin pathway. Cell Proliferation, 42: 721–730. doi: 10.1111/j.1365-2184.2009.00639.x
- Issue online: 27 OCT 2009
- Version of Record online: 25 AUG 2009
- Received 30 December 2008; revision accepted 17 April 2009
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.