Suppression of Bone Formation and Resorption by the Deletion of Complex Gangliosides

Gangliosides regulate bone formation and resorption. Bone formation is reduced in mice lacking ganglioside GM2/GD2 synthase due to a decrease in osteoblasts. However, the effects of the loss of complex gangliosides by the deletion of both GM2/GD2 and GD3 synthases are unknown. Therefore, we investigated whether deletion of complex gangliosides in mice affected bone metabolism.

Twenty-six double-knockout mice lacking both GM2/GD2 and GD3 synthases (dKO) and 30 wild-type (WT) mice as controls were used. The mass of cancellous bone and bone strength in femurs were determined using three-dimensional micro-computed tomography and three-point bending test, respectively. Bone formation and resorption were assessed using histomorphometrical analysis with hematoxylin and eosin, and tartrate-resistant acid phosphatase (TRAP), respectively. Osteoblast proliferation was determined by bromodeoxyuridine assay and the differentiation into osteoclasts by TRAP staining; mRNA levels of osteoclast differentiation markers [nuclear factor of activated T-cells, cytoplasmic 1 (Nfatc1); Trap; and cathepsin K (Ctsk)] were also determined.

Bone mass increased in dKO mice, while bone formation and resorption decrease. In terms of bone strength, breaking displacement significantly increased in dKO mice. Furthermore, the proliferation of osteoblasts was suppressed, and the number of TRAP-positive multinucleated cells was reduced in dKO mice. Treatment with receptor activator of NF-[Formula: see text]B ligand significantly reduced Nfatc1, Trap and Ctsk mRNA levels in macrophages from dKO mice.

Bone formation and resorption were reduced by the deletion of genes for complex gangliosides. The slight increase in bone strength in dKO mice may be due to the cancellous bone volume increase in these mice.