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Deletion of Gb3 Synthase in Mice Resulted in the Attenuation of Bone Formation via Decrease in Osteoblasts
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- Kazunori Hamamura
- Department of Pharmacology, School of Dentistry, Aichi Gakuin University, Nagoya 464-8650, Japan
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- Kosuke Hamajima
- Department of Pharmacology, School of Dentistry, Aichi Gakuin University, Nagoya 464-8650, Japan
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- Shoyoku Yo
- Department of Pharmacology, School of Dentistry, Aichi Gakuin University, Nagoya 464-8650, Japan
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- Yoshitaka Mishima
- Department of Pharmacology, School of Dentistry, Aichi Gakuin University, Nagoya 464-8650, Japan
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- Koichi Furukawa
- Department of Biomedical Sciences, Chubu University College of Life and Health Sciences, Kasugai, Aichi 487-8501, Japan
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- Makoto Uchikawa
- Japanese Red Cross Tokyo Blood Center, Tokyo 162-8639, Japan
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- Yuji Kondo
- Department of Biochemistry II, Nagoya University Graduate School of Medicine, Nagoya 464-8650, Japan
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- Hironori Mori
- Department of Pharmacology, School of Dentistry, Aichi Gakuin University, Nagoya 464-8650, Japan
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- Hisataka Kondo
- Department of Pharmacology, School of Dentistry, Aichi Gakuin University, Nagoya 464-8650, Japan
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- Kenjiro Tanaka
- Department of Pharmacology, School of Dentistry, Aichi Gakuin University, Nagoya 464-8650, Japan
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- Ken Miyazawa
- Department of Orthodontics, School of Dentistry, Aichi Gakuin University, Nagoya 464-8650, Japan
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- Shigemi Goto
- Department of Orthodontics, School of Dentistry, Aichi Gakuin University, Nagoya 464-8650, Japan
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- Akifumi Togari
- Department of Pharmacology, School of Dentistry, Aichi Gakuin University, Nagoya 464-8650, Japan
Description
<jats:p>Glycosphingolipids are known to play a role in developing and maintaining the integrity of various organs and tissues. Among glycosphingolipids, there are several reports on the involvement of gangliosides in bone metabolism. However, there have been no reports on the presence or absence of expression of globo-series glycosphingolipids in osteoblasts and osteoclasts, and the involvement of their glycosphingolipids in bone metabolism. In the present study, we investigated the presence or absence of globo-series glycosphingolipids such as Gb3 (globotriaosylceramide), Gb4 (globoside), and Gb5 (galactosyl globoside) in osteoblasts and osteoclasts, and the effects of genetic deletion of Gb3 synthase, which initiates the synthesis of globo-series glycosphingolipids on bone metabolism. Among Gb3, Gb4, and Gb5, only Gb4 was expressed in osteoblasts. However, these glycosphingolipids were not expressed in pre-osteoclasts and osteoclasts. Three-dimensional micro-computed tomography (3D-μCT) analysis revealed that femoral cancellous bone mass in Gb3 synthase-knockout (Gb3S KO) mice was lower than that in wild type (WT) mice. Calcein double labeling also revealed that bone formation in Gb3S KO mice was significantly lower than that in WT mice. Consistent with these results, the deficiency of Gb3 synthase in mice decreased the number of osteoblasts on the bone surface, and suppressed mRNA levels of osteogenic differentiation markers. On the other hand, osteoclast numbers on the bone surface and mRNA levels of osteoclast differentiation markers in Gb3S KO mice did not differ from WT mice. This study demonstrated that deletion of Gb3 synthase in mice decreases bone mass via attenuation of bone formation.</jats:p>
Journal
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- International Journal of Molecular Sciences
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International Journal of Molecular Sciences 20 (18), 4619-, 2019-09-18
MDPI AG
