Response of bone marrow stromal cells to adipogenic antagonists.
Response of bone marrow stromal cells to adipogenic antagonists.
复制标题
骨髓基质细胞对脂肪形成拮抗剂的反应。
DOI：
10.1128/mcb.9.11.4587-4595.1989
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发表时间：
1989
影响因子：
5.3
通讯作者：
Wang,CS
中科院分区：
文献类型：
--
作者：
Gimble,JM;Dorheim,MA;Cheng,Q;Pekala,P;Enerback,S;Ellingsworth,L;Kincade,PW;Wang,CS
脂肪细胞是体内骨髓基质的主要组成部分，在淋巴造血中可能发挥积极作用。早期的研究表明，骨髓基质细胞克隆BMS2除了具有明确的支持B淋巴生成的能力外，还能够在体外分化脂肪细胞。我们现在证明，这种功能性骨髓基质细胞克隆的脂肪生成过程可以被白细胞介素-la、肿瘤坏死因子和转化生长因子β所抑制。通过形态学标准和中性脂质含量分析评估，将前脂肪细胞BMS2暴露于这些药物中可以阻断脂肪细胞分化的诱导。白细胞介素-lα和肿瘤坏死因子均可引起c-fos、c-jun和乙脑稳态mRNA水平的短暂快速升高。当添加到分化的脂肪细胞中时，这三种细胞因子继续作为脂肪生成拮抗剂。脂肪细胞特异性酶脂蛋白脂肪酶活性的浓度和时间依赖性降低表明了这一点。这些酶活性的变化与脂蛋白脂肪酶mRNA稳态水平的降低直接相关。另一种脂肪细胞分化的RNA标记物（脂肪素）受脂肪生成拮抗剂的影响较小。这可能反映了与脂蛋白脂肪酶相比，该mRNA转录物的半衰期更长。结果表明，骨髓基质细胞的分化状态可受外源因子的调控。这也是第一次报道转化生长因子β调节脂蛋白脂肪酶的活性。这些数据表明，在淋巴造血的整体背景下，这些细胞因子在体内的潜在生理作用。
Adipocytes constitute a major part of the bone marrow stroma in vivo and may play an active role in lymphohematopoiesis. Earlier studies had shown that the bone marrow stromal cell clone BMS2 was capable of adipocyte differentiation in vitro, in addition to its well-defined ability to support B lymphopoiesis. We now demonstrate that the process of adipogenesis in this functional bone marrow stromal cell clone can be inhibited by the cytokines interleukin-la, tumor necrosis factor, and transforming growth factor β. Exposure of preadipocyte BMS2 cells to these agents blocked the induction of adipocyte differentiation as assessed by morphologic criteria and analysis of the neutral lipid content. Both interleukin-lα and tumor necrosis factor elicited a rapid transient elevation in the steady-state mRNA levels of c-fos, c-jun, and JE. When added to differentiated adipocytes, the three cytokines continued to act as adipogenic antagonists. This was indicated by concentration- and time-dependent decreases in the activity of an adipocyte-specific enzyme, lipoprotein lipase. These changes in enzyme activity correlated directly with a decrease in steady-state levels of lipoprotein lipase mRNA. Another RNA marker of adipocyte differentiation (adipsin) was less influenced by the adipogenic antagonists. This may reflect the longer half-life of this mRNA transcript compared with those of lipoprotein lipase. Our results dramatically demonstrate that the differentiation state of bone marrow stromal cells can be modulated by exogenous factors in vitro. It is also the first report that transforming growth factor β regulates the activity of lipoprotein lipase. These data suggest potential physiologic actions for these cytokines in vivo within the overall context of lymphohematopoiesis.