Increased adipogenesis of osteoporotic human-mesenchymal stem cells (MSCs) is characterized by impaired leptin action
Increased adipogenesis of osteoporotic human-mesenchymal stem cells (MSCs) is characterized by impaired leptin action
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DOI：
10.1002/jcb.21516
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发表时间：
2008-03-01
影响因子：
4
通讯作者：
Rodriguez, J. Pablo
中科院分区：
文献类型：
--
作者：
Astudillo, Pablo;Rios, Susana;Rodriguez, J. Pablo
骨髓含有间充质干细胞（MSC），可分化为成骨和成脂谱系。年龄相关性骨质疏松症的骨体积减少伴随着骨髓脂肪组织的增加，这一事实暗示了脂肪形成过程在骨丢失中的重要性。我们以前观察到，从控制和骨质疏松症妇女的MSC显示其分化成骨和成脂途径的能力的差异。体外研究表明，骨髓基质细胞对瘦素有反应，瘦素增加骨髓基质细胞的增殖、向成骨细胞的分化和矿化结节的数量，但抑制骨髓基质细胞向脂肪细胞的分化。本报告的目的是研究瘦素对对照和骨质疏松症MSC的直接作用，分析瘦素对骨质疏松症的保护作用是否可以通过抑制脂肪细胞分化来表达。在不存在或存在62.5 nM瘦素的情况下，使来自对照和肥胖供体的MSC经受脂肪形成条件。采用流式细胞术、Western blot和RT-PCR分别检测脂肪细胞数、过氧化物酶体增殖物激活受体γ（PPARgamma）蛋白和mRNA的含量以及瘦素（leptin）mRNA的含量。结果表明，对照和增生MSC在其成脂潜力方面不同，如活性PPAR γ蛋白的表达所示。瘦素只对对照间充质干细胞产生抗脂肪形成作用，增加了无活性磷酸化PPAR γ蛋白的比例。最后，在脂肪细胞的脂肪形成过程中获得的结果表明，这一过程是异常的，不仅是因为脂肪细胞数量增加，但因为受损的瘦素细胞的反应。
The bone marrow contains mesenchymal stem cells (MSCs) that differentiate to the osteogenic and adipogenic lineages. The fact that the decrease in bone volume of age-related osteoporosis is accompanied by an increase in marrow adipose tissue implies the importance that the adipogenic process may have in bone loss. We previously observed that MSCs from control and osteoporotic women showed differences in their capacity to differentiate into the osteogenic and adipogenic pathways. In vitro studies indicate that bone marrow stromal cells are responsive to leptin, which increases their proliferation, differentiation to osteoblasts, and the number of mineralized nodules, but inhibits their differentiation to adipocytes. The aim of the present report was to study the direct effect of leptin on control and osteoporotic MSCs analyzing whether the protective effect of leptin against osteoporosis could be expressed by inhibition of adipocyte differentiation. MSCs from control, and osteoporotic donors were subjected to adipogenic conditions, in the absence or in the presence of 62.5 nM leptin. The number of adipocytes, the content of PPAR gamma protein, and mRNA, and leptin mRNA were measured by flow cytometry, Western blot, and RT-PCR, respectively. Results indicate that control and osteoporotic MSCs differ in their adipogenic potential as shown by expression of active PPAR gamma protein. Leptin exerted an antiadipogenic effect only on control MSCs increasing the proportion of inactive phosphorylated PPAR gamma protein. Finally, results obtained during adipogenesis of osteoporotic cells suggest that this process is abnormal not only because of increased adipocyte number, but because of impaired leptin cells response.