N-acetylglucosamine suppresses osteoclastogenesis in part through the promotion ofO-GlcNAcylation.
Osteoclasts are the only cells in an organism capable of resorbing bone. These cells differentiate from monocyte/macrophage lineage cells upon stimulation by receptor activator of NF-κB ligand (RANKL). On the other hand, osteoclastogenesis is reportedly suppressed by glucose via the downregulation of NF-κB activity through suppression of reactive oxygen species generation. To examine whether other sugars might also affect osteoclast development, we compared the effects of monomeric sugars (glucose, galactose,N-acetylglucosamine (GlcNAc), andN-acetylgalactosamine (GalNAc)) on the osteoclastogenesis of murine RAW264 cells. Our results demonstrated that, in addition to glucose, both GlcNAc and GalNAc, which each have little effect on the generation of reactive oxygen species, suppress osteoclastogenesis. We hypothesized that GlcNAc might affect osteoclastogenesis through the upregulation ofO-GlcNAcylation and showed that GlcNAc increases globalO-GlcNAcylation, thereby suppressing the RANKL-dependent phosphorylation of NF-κB p65. Furthermore, an inhibitor ofN-acetyl-β-D-glucosaminidase,O-(2-acetamido-2-deoxy-D-glucopyranosylidene) aminoN-phenylcarbamate (PUGNAc), which also increasesO-GlcNAcylation, suppressed the osteoclastogenesis of RAW264 cells and that of human peripheral blood mononuclear cells. Together, these data suggest that GlcNAc suppresses osteoclast differentiation in part through the promotion of O-GlcNAcylation.
Faculty of Pharmaceutical Sciences, Josai University, Saitama 350-0295, Japan.
Tomoharu
T
Takeuchi
Faculty of Pharmaceutical Sciences, Josai University, Saitama 350-0295, Japan.
Moyuko
M
Nagasaka
Faculty of Pharmaceutical Sciences, Josai University, Saitama 350-0295, Japan.
Miyuki
M
Shimizu
Faculty of Pharmaceutical Sciences, Josai University, Saitama 350-0295, Japan.
Mayumi
M
Tamura
Faculty of Pharmaceutical Sciences, Josai University, Saitama 350-0295, Japan.
Yoichiro
Y
Arata
Gal, galactose; GalNAc, N-acetylgalactosamine; Glc, glucose; GlcNAc; GlcNAc, N-acetylglucosamine; M-CSF, macrophage colony-stimulating factor; N-acetylglucosamine; NF-κB; NF-κB, nuclear factor-κB; O-GlcNAcylation; Osteoclast; PBMC, peripheral blood mononuclear cell; PUGNAc, O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenylcarbamate; RANKL, receptor activator of nuclear factor-κB ligand; ROS, reactive oxygen species; TRAP, tartrate-resistant acid phosphatase; UDP, uridine diphosphate; sRANKL, soluble receptor activator of nuclear factor-κB ligand