Deficiency of GD3 Synthase in Mice Resulting in the Attenuation of Bone Loss with Aging

Int J Mol Sci. 2019 Jun 10;20(11):2825. doi: 10.3390/ijms20112825.

Abstract

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-μCT) 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.

Keywords: bone metabolism; gangliosides; glycosphingolipids; glycosylation.

MeSH terms

  • Aging / pathology*
  • Animals
  • Bone Resorption / genetics*
  • Cells, Cultured
  • Gangliosides / metabolism
  • Mice
  • Osteoclasts / metabolism
  • Osteoclasts / pathology
  • Osteogenesis
  • RANK Ligand / metabolism
  • RAW 264.7 Cells
  • Sialyltransferases / deficiency
  • Sialyltransferases / genetics*

Substances

  • Gangliosides
  • RANK Ligand
  • Sialyltransferases
  • alpha-N-acetylneuraminate alpha-2,8-sialyltransferase