Contribution of Glucosylceramide Synthase to the Proliferation of Mouse Osteoblasts.

Autor:	Mishima Y; Department of Pharmacology, School of Dentistry, Aichi Gakuin University, Nagoya, Japan.; Department of Orthodontics, School of Dentistry, Aichi Gakuin University, Nagoya, Japan., Hamamura K; Department of Pharmacology, School of Dentistry, Aichi Gakuin University, Nagoya, Japan; hamak@dpc.agu.ac.jp., Kato H; Department of Pharmacology, School of Dentistry, Aichi Gakuin University, Nagoya, Japan.; Department of Orthodontics, School of Dentistry, Aichi Gakuin University, Nagoya, Japan., Furukawa K; Department of Biomedical Sciences, Chubu University College of Life and Health Sciences, Kasugai, Japan., Tashima Y; Department of Molecular Biochemistry, Nagoya University Graduate School of Medicine, Nagoya, Japan., Okajima T; Department of Molecular Biochemistry, Nagoya University Graduate School of Medicine, Nagoya, Japan., Kondo H; Department of Pharmacology, School of Dentistry, Aichi Gakuin University, Nagoya, Japan., Sato T; Department of Orthodontics, School of Dentistry, Aichi Gakuin University, Nagoya, Japan., Miyazawa K; Department of Orthodontics, School of Dentistry, Aichi Gakuin University, Nagoya, Japan., Goto S; Department of Orthodontics, School of Dentistry, Aichi Gakuin University, Nagoya, Japan., Togari A; Department of Pharmacology, School of Dentistry, Aichi Gakuin University, Nagoya, Japan.
Jazyk:	angličtina
Zdroj:	In vivo (Athens, Greece) [In Vivo] 2021 Nov-Dec; Vol. 35 (6), pp. 3111-3123.
DOI:	10.21873/invivo.12606
Abstrakt:	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. (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)
Databáze:	MEDLINE
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