葡萄糖神经酰胺合成酶对小鼠成骨细胞增殖的贡献。
Contribution of Glucosylceramide Synthase to the Proliferation of Mouse Osteoblasts.
机构信息
Department of Pharmacology, School of Dentistry, Aichi Gakuin University, Nagoya, Japan.
Department of Orthodontics, School of Dentistry, Aichi Gakuin University, Nagoya, Japan.
出版信息
In Vivo. 2021 Nov-Dec;35(6):3111-3123. doi: 10.21873/invivo.12606.
BACKGROUND/AIM: Glycosphingolipids are known to be involved in bone metabolism. However, their roles and regulatory mechanisms in osteoblast proliferation are largely unknown. In this study, we examined the effects of inhibitors of glucosylceramide synthase (GCS), which is responsible for the generation of all glycosphingolipids, on osteoblast proliferation.
MATERIALS AND METHODS
We analyzed the expression of glycosphingolipids and cell growth in MC3T3-E1 mouse osteoblast cells treated with the GCS inhibitors miglustat, D-PDMP and D-PPMP. We also conducted microarray analysis and RNA interference to identify genes involved in cell growth regulated by GCS.
RESULTS
Glycosphingolipids GD1a and Gb4 expressed in MC3T3-E1 cells, were suppressed by GCS inhibitors. Furthermore, the proliferation of MC3T3-E1 cells was suppressed by the inhibitors. Using microarray analysis, we predicted nine genes (Fndc1, Acta2, Igfbp5, Cox6a2, Cth, Mymk, Angptl6, Mab21l2, and Igsf10) suppressed by all three inhibitors. Furthermore, partial silencing of Angptl6 by RNA interference reduced MC3T3-E1 cell growth.
CONCLUSION
These results show that GCS regulates proliferation through Angptl6 in osteoblasts.
背景/目的：糖脂是已知参与骨代谢的物质。然而，它们在成骨细胞增殖中的作用和调节机制在很大程度上尚不清楚。在这项研究中，我们研究了负责所有糖脂生成的葡萄糖神经酰胺合酶（GCS）抑制剂对成骨细胞增殖的影响。
材料和方法
我们分析了用 GCS 抑制剂米格列醇、D-PDMP 和 D-PPMP 处理的 MC3T3-E1 小鼠成骨细胞中糖脂的表达和细胞生长情况。我们还进行了微阵列分析和 RNA 干扰，以鉴定受 GCS 调节的细胞生长相关基因。
结果
在 MC3T3-E1 细胞中表达的糖脂 GD1a 和 Gb4 被 GCS 抑制剂抑制。此外，抑制剂还抑制了 MC3T3-E1 细胞的增殖。通过微阵列分析，我们预测了被三种抑制剂都抑制的九个基因（Fndc1、Acta2、Igfbp5、Cox6a2、Cth、Mymk、Angptl6、Mab21l2 和 Igsf10）。此外，RNA 干扰对 Angptl6 的部分沉默降低了 MC3T3-E1 细胞的生长。
结论
这些结果表明，GCS 通过成骨细胞中的 Angptl6 调节增殖。
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