Contribution of Glucosylceramide Synthase to the Proliferation of Mouse Osteoblasts
Contribution of Glucosylceramide Synthase to the Proliferation of Mouse Osteoblasts
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DOI：
10.21873/invivo.12606
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发表时间：
2021-11-01
期刊：
影响因子：
2.3
通讯作者：
Togari, Akifumi
中科院分区：
文献类型：
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作者：
Mishima, Yoshitaka;Hamamura, Kazunori;Togari, Akifumi
背景/目的：鞘糖脂参与骨代谢。然而，它们在成骨细胞增殖中的作用和调控机制在很大程度上是未知的。在这项研究中，我们检测了葡萄糖神经酰胺合成酶（GCS）抑制剂对成骨细胞增殖的影响，GCS负责生成所有鞘糖脂。材料与方法：分析GCS抑制剂米格司他、D-PDMP和D-PPMP对MC3T3-E1小鼠成骨细胞的鞘糖脂表达和细胞生长的影响。我们还通过微阵列分析和RNA干扰来鉴定GCS调控细胞生长的相关基因。结果：GCS抑制剂抑制MC3T3-E1细胞中鞘糖脂GD1a和Gb4的表达。此外，抑制MC3T3-E1细胞的增殖。通过芯片分析，我们预测了9个基因（Fndc1、Acta2、Igfbp5、Cox6a2、Cth、Mymk、Angptl6、Mab21l2和Igsf10）被所有三种抑制剂抑制。此外，通过RNA干扰部分沉默Angptl6可降低MC3T3-E1细胞的生长。结论：GCS通过Angptl6调控成骨细胞增殖。
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.