Arsenic trioxide promotes senescence and regulates the balance of adipogenic and osteogenic differentiation in human mesenchymal stem cells.
Arsenic trioxide (ATO) as an anti-tumor drug could induce differentiation and apoptosis in tumor cells. Mesenchymal stem cells (MSCs) play important roles in the hematogenesis of bone marrow. Many reports have shown that the disorder of MSC adipogenic and osteogenic differentiation occurs in some diseases. However, reports about the effects of ATO on MSCs are limited. In this study, we found that 1 μM ATO promoted MSC senescence mainly through p21, although it had no effect on apoptosis at this dose. Furthermore, ATO promoted adipogenic differentiation, but inhibited osteogenic differentiation in MSCs. Our study also showed that CCAAT/enhancer-binding protein alpha C/EBPα and peroxisome proliferator-activated receptor gamma PPARγ might be involved in the regulation of adipogenic and osteogenic differentiation induced by ATO. Our results indicated that ATO may exert an anti-tumor effect by influencing bone marrow micro-environment. Moreover, it may regulate the adipogenic and osteogenic differentiation of MSCs.
Department of Histology and Embryology, Harbin Medical University, Harbin, China.
Huanchen
H
Cheng
Lin
L
Qiu
Hao
H
Zhang
Mei
M
Cheng
Wei
W
Li
Xuefei
X
Zhao
Keyu
K
Liu
Lei
L
Lei
Jun
J
Ma
D050156:Adipogenesis / Q000187:drug effects*; D000375:Aging / Q000187:drug effects; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D001854:Bone Marrow Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000187:drug effects / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects*; D010087:Oxides / Q000494:pharmacology*; D047495:PPAR gamma / Q000187:drug effects / Q000378:metabolism
D001152:Arsenicals; D022763:CCAAT-Enhancer-Binding Protein-alpha; D050759:Cyclin-Dependent Kinase Inhibitor p21; D010087:Oxides; D047495:PPAR gamma; D000077237:Arsenic Trioxide