グロボ系スフィンゴ糖脂質欠損マウスでは、骨芽細胞の減少により骨形成が低下する

抄録

Purpose: Globo-series glycosphingolipids have not only been used as markers for stem cells and tumors but are also considered to regulate maintain stemness and immune system. However, there have no reports on the involvement of globo-series glycosphingolipids in bone metabolism. In this study, we investigated the effects of genetic deletion of Gb3 synthase, which initiates the synthesis of globo-seires glycosphingolipids on bone metabolism.

Material & Methods: We examined expression levels of globo-series glycosphingolipids (Gb3, Gb4, and Gb5) in MC3T3 E1 mouse osteoblast-like cells and SaM-1 human osteoblast cells using flow cytometry. To determine whether globo-series glycosphingolipids are involved in bone metabolism, we analyzed bone phenotype of Gb3 shynthase-knockout (Gb3S KO) mice using μCT. Furthermore, we conducted a calcein double labeling method to evaluate bone formation.

Results & Conclusion: Among Gb3, Gb4, and Gb5, only Gb4 was expressed in osteoblasts. μCT analysis revealed that femoral cancellous bone mass in 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 lower that that in WT mice. We demonstrated that Gb4 is expressed in osteoblasts, and globo-series glycosphingolipids regulate bone mass through bone formation.