Effects of arachidonic acid on the concentration of hydroxyeicosatetraenoic acids in culture media of mesenchymal stromal cells differentiating into adipocytes or osteoblasts
Effects of arachidonic acid on the concentration of hydroxyeicosatetraenoic acids in culture media of mesenchymal stromal cells differentiating into adipocytes or osteoblasts
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DOI：
10.1007/s12263-013-0375-1
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发表时间：
2014-01-01
影响因子：
3.5
通讯作者：
Manuel Quesada-Gomez, Jose
中科院分区：
文献类型：
--
作者：
Casado-Diaz, Antonio;Ferreiro-Vera, Carlos;Manuel Quesada-Gomez, Jose
多不饱和脂肪酸（PUFA）衍生的代谢产物可以调节间充质基质细胞（MSC）的分化。这些细胞可以分化成不同的细胞类型，包括脂肪细胞和成骨细胞。衰老有利于骨髓MSC向前者分化，导致与骨质疏松症等病理相关的骨密度损失。ω-6花生四烯酸（AA）比ω-3二十碳五烯酸（EPA）和二十二碳六烯酸（DHA）更有利于MSC脂肪生成。在这项工作中，我们研究了这两个PUFA的联合行动。因此，未诱导和诱导成脂肪细胞或成骨细胞的MSC用20 μ M的每种PUFA（AA、AA + DHA或AA + EPA）处理。成骨和成脂分子标记物的表达，alox 15 b脂氧合酶基因的表达和5-，8-，11-，12-和15-羟基二十碳四烯酸（HETE）来源于AA代谢的培养基中进行了测定。结果表明，AA的脂肪形成诱导不受EPA和DHA的联合存在的抑制。事实上，两者都增加了AA对MSC分化为成骨细胞的成脂作用。不同的HETE浓度在补充AA的培养物中增加，尽管在诱导分化的培养物中这种浓度较低，主要在诱导后第21天。此外，HETE浓度的降低与alox 15 b基因的较高表达相关。这些结果突出了未诱导和诱导MSC分化为脂肪细胞和成骨细胞的PUFA代谢差异，以及脂氧合酶基因表达在脂肪形成诱导中的相关作用。
Metabolites derived from the polyunsaturated fatty acids (PUFA) may modulate the mesenchymal stromal cell (MSC) differentiation. Such cells can differentiate into different cellular types, including adipocytes and osteoblasts. Aging favors the bone marrow MSC differentiation toward the former, causing a loss of bone density associated with pathologies like osteoporosis. The omega-6 arachidonic acid (AA) favors MSC adipogenesis to a greater extent than omega-3 eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). In this work, we study the joint action of both PUFA. Thus, not induced and induced to adipocyte or osteoblast MSC were treated with 20 mu M of each PUFA (either AA, AA + DHA or AA + EPA). The expression of osteogenic and adipogenic molecular markers, the alox15b lipoxygenase gene expression and the 5-, 8-, 11-, 12-and 15-hydroxyeicosatetraenoic acids (HETE) derived from the AA metabolism in the culture media were determined. The results show that the adipogenesis induction of AA is not suppressed by the joint presence of EPA and DHA. In fact, both increased the adipogenic effect of AA on MSC differentiated into osteoblasts. The different HETE concentrations increased in cultures supplemented with AA, albeit such concentrations were lower in the cultures induced to differentiate, mainly at day 21 after the induction. Furthermore, the reduction in the HETE concentration was correlated with a higher expression of the alox15b gene. These results highlight the PUFA metabolism differences between uninduced and induced MSC to differentiate into adipocytes and osteoblasts, besides the relevant role of the lipoxygenase gene expression in adipogenesis induction.