Induction of adipocyte-like phenotype in human mesenchymal stem cells by hypoxia
Induction of adipocyte-like phenotype in human mesenchymal stem cells by hypoxia
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DOI：
10.1634/stemcells.2004-0038
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发表时间：
2004-01-01
期刊：
影响因子：
5.2
通讯作者：
Zachar, V
中科院分区：
文献类型：
--
作者：
Fink, T;Abildtrup, L;Zachar, V
人骨髓间充质干细胞（hMSCs）具有沿着几条途径分化形成骨、软骨、肌腱、肌肉和脂肪组织的能力。成体hMSC在体内驻留在骨髓中的小生境中，其中氧浓度远低于环境空气，这是最常见的实验室条件。本文报道的研究旨在确定氧是否在hMSCs分化为脂肪细胞中起作用。事实上，当暴露于仅含1%氧的气氛中时，观察到具有细胞质脂质内含物的脂肪细胞样表型的形成。实时荧光定量逆转录聚合酶链反应检测缺氧对脂肪细胞特异性基因表达的影响。有趣的是，脂肪生成的两个中心调节因子--转录因子过氧化物酶体增殖物激活受体γ 2（PPAR-gamma 2）和ADD 1/SREBP 1c--都没有被诱导。此外，缺氧对早期（脂蛋白脂酶）或晚期（aP 2）标记基因的转录没有任何影响。同样的道理，成熟脂肪细胞特异性基因瘦素和亲脂素都没有发现对治疗有反应。然而，在PPAR-γ诱导的血管生成素相关基因PGAR中观察到了高水平的诱导。因此，缺乏脂肪细胞特异性转录模式表明，尽管脂质积累，但真正的成脂分化并没有发生。总之，缺氧似乎发挥了有效的脂肪生成作用，独立于PPAR-gamma 2成熟途径。
Human mesenchymal stem cells (hMSCs) have the capacity to differentiate along several pathways to form bone, cartilage, tendon, muscle, and adipose tissues. The adult hMSCs reside in vivo in the bone marrow in niches where oxygen concentration is far below the ambient air, which is the most commonly encountered laboratory condition. The study reported here was designed to determine whether oxygen has a role in the differentiation of hMSCs into adipocytes. Indeed, when exposed to atmosphere containing only 1 % of oxygen, the formation of adipocyte-like phenotype with cytoplasmic lipid inclusions was observed. The effect of hypoxia on the expression of adipocyte-specific genes was determined by real-time reverse transcription polymerase chain reaction. Interestingly, neither of the two central regulators of adipogene-sis-the transcription factors peroxisome proliferator-activated receptor gamma2 (PPAR-gamma2) and ADD1/SREBP1c-was induced. Furthermore, hypoxia did not have any effect on the transcription of early (lipoprotein lipase) or late (aP2) marker genes. By the same token, neither of the mature adipocyte-specific genes-leptin and adipophilin-was found responsive to the treatment. High level of induction, however, was observed with the PPAR-gamma-induced angiopoietin-related gene, PGAR. The lack of an adipocyte-specific transcription pattern thus indicates that despite accumulation of the lipid, true adipogenic differentiation did not take place. In conclusion, hypoxia appears to exert a potent lipogenic effect independent of PPAR-gamma2 maturation pathway.