Contribution of Glucosylceramide Synthase to the Proliferation of Mouse Osteoblasts.

Yoshitaka Mishima, Kazunori Hamamura, Hanami Kato, Koichi Furukawa, Yuko Tashima, Tetsuya Okajima, Hisataka Kondo, Takuma Sato, Ken Miyazawa, Shigemi Goto, Akifumi Togari

In vivo (Athens, Greece) 2021 Nov-Dec

filter terms:

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. 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. 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. These results show that GCS regulates proliferation through Angptl6 in osteoblasts. Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Citation

Yoshitaka Mishima, Kazunori Hamamura, Hanami Kato, Koichi Furukawa, Yuko Tashima, Tetsuya Okajima, Hisataka Kondo, Takuma Sato, Ken Miyazawa, Shigemi Goto, Akifumi Togari. Contribution of Glucosylceramide Synthase to the Proliferation of Mouse Osteoblasts. In vivo (Athens, Greece). 2021 Nov-Dec;35(6):3111-3123