Deficiency of GD3 Synthase in Mice Resulting in the Attenuation of Bone Loss with Aging
Deficiency of GD3 Synthase in Mice Resulting in the Attenuation of Bone Loss with Aging
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DOI：
10.3390/ijms20112825
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发表时间：
2019-06-01
影响因子：
5.6
通讯作者：
Togari, Akifumi
中科院分区：
文献类型：
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作者：
Yo, Shoyoku;Hamamura, Kazunori;Togari, Akifumi
神经节苷脂在几乎所有组织和细胞中广泛表达，并且也被认为是各种器官和组织的发育和维持所必需的。然而，很少有人知道它们在骨代谢中的作用。在这项研究中，我们研究了神经节苷脂D3（GD 3）合成酶，这是负责所有b系列神经节苷脂的产生，对骨代谢的影响的基因缺失。虽然b系列神经节苷脂在成骨细胞中不表达，但这些神经节苷脂在前破骨细胞中表达。然而，这些神经节苷脂的表达减少后，诱导破骨细胞生成的核因子κ-B配体受体激活剂（RANKL）。三维显微计算机断层扫描（3D-CT）分析显示，在40周龄时，GD 3酶敲除（GD 3S KO）小鼠的股骨松质骨质量高于野生型（WT）小鼠，尽管在15周龄时GD 3S KO和WT小鼠之间没有差异。尽管GD 3S KO小鼠的骨形成参数（成骨细胞数量/骨表面和成骨细胞表面/骨表面）与WT小鼠无差异，但GD 3S KO小鼠的骨吸收参数（破骨细胞数量/骨表面和破骨细胞表面/骨表面）在40周龄时显著低于WT小鼠。总的来说，这项研究表明，GD 3合酶的缺失减弱了随着年龄的增长而出现的骨丢失。
Gangliosides are widely expressed in almost all tissues and cells and are also considered to be essential in the development and maintenance of various organs and tissues. However, little is known about their roles in bone metabolism. In this study, we investigated the effects of genetic deletion of ganglioside D3 (GD3) synthase, which is responsible for the generation of all b-series gangliosides, on bone metabolism. Although b-series gangliosides were not expressed in osteoblasts, these gangliosides were expressed in pre-osteoclasts. However, the expression of these gangliosides was decreased after induction of osteoclastogenesis by receptor activator of nuclear factor kappa-B ligand (RANKL). Three-dimensional micro-computed tomography (3D-CT) analysis revealed that femoral cancellous bone mass in GD3 synthase-knockout (GD3S KO) mice was higher than that in wild type (WT) mice at the age of 40 weeks, although there were no differences in that between GD3S KO and WT mice at 15 weeks old. Whereas bone formation parameters (osteoblast numbers/bone surface and osteoblast surface/bone surface) in GD3S KO mice did not differ from WT mice, bone resorption parameters (osteoclast numbers/bone surface and osteoclast surface/bone surface) in GD3S KO mice became significantly lower than those in WT mice at 40 weeks of age. Collectively, this study demonstrates that deletion of GD3 synthase attenuates bone loss that emerges with aging.