Arsenic trioxide promotes senescence and regulates the balance of adipogenic and osteogenic differentiation in human mesenchymal stem cells
Arsenic trioxide promotes senescence and regulates the balance of adipogenic and osteogenic differentiation in human mesenchymal stem cells
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DOI：
10.1093/abbs/gmq130
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发表时间：
2011-01-01
影响因子：
3.7
通讯作者：
Ma, Jun
中科院分区：
文献类型：
--
作者：
Cheng, Huanchen;Qiu, Lin;Ma, Jun
三氧化二砷（ATO）作为抗肿瘤药物可诱导肿瘤细胞分化和凋亡。间充质干细胞（MSCs）在骨髓造血中起着重要的作用。许多报道表明，间充质干细胞成脂和成骨分化障碍发生在某些疾病中。然而，ATO对间充质干细胞影响的报道有限。在本研究中，我们发现1 μ M ATO主要通过p21促进MSC衰老，但在该剂量下对细胞凋亡没有影响。此外，ATO促进了MSCs的成脂分化，但抑制了成骨分化。我们的研究还表明，CCAAT/增强子结合蛋白α C/EBP α和过氧化物酶体增殖物激活受体PPAR γ可能参与了ATO诱导的成脂和成骨分化的调控。结果表明，ATO可能通过影响骨髓微环境发挥抗肿瘤作用。此外，它还可能调节间充质干细胞的成脂和成骨分化。
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 mu M 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/EBP alpha and peroxisome proliferator-activated receptor gamma PPAR gamma 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.