Complex effect of continuous curcumin exposure on human bone marrow-derived mesenchymal stem cell regenerative properties through matrix metalloproteinase regulation.

ABSTRACT

Curcumin has been reported to be beneficial for cancers, cardiovascular and neurodegenerative diseases, based on its anti-oxidative, anti-inflammation, anti-tumorigenic and neuroprotective properties. With its high-dose application, curcumin toxicity to systemic tissues is a reasonable concern. Here, we report the responses of human bone marrow-derived mesenchymal stem cells (hBM-MSCs) to continuous curcumin exposure. hBM-MSCs were treated with 0.01-100 µmol/L curcumin continuously in vitro for 7 days. 25 µmol/L curcumin or above significantly attenuated hBM-MSC maintenance, whereas 10 µmol/L curcumin reduced hBM-MSC proliferation and hindered their migration with increasing cell apoptosis. Besides, 5 µmol/L curcumin treatment inhibited hBM-MSC adipogenic differentiation, but enhanced osteogenic differentiation, which depended on matrix metalloproteinase (MMP)-13 expression and activity. Furthermore, curcumin treatment reduced MMP1 expression but up-regulated the immunomodulatory gene IDO1 expression. In summary, this study revealed the complex effects of continuous curcumin exposure on hBM-MSC maintenance and regenerative properties through MMP regulation. Given the complex effects of curcumin, its use for biomedical purposes should be carefully considered in treatment length and dosage.