N-acetylglucosamine suppresses osteoclastogenesis in part through the promotion of O-GlcNAcylation
Autor: | Tomoharu Takeuchi, Moyuko Nagasaka, Mayumi Tamura, Yoichiro Arata, Miyuki Shimizu |
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Jazyk: | angličtina |
Předmět: |
0301 basic medicine
PBMC peripheral blood mononuclear cell lcsh:Diseases of the musculoskeletal system GlcNAc Endocrinology Diabetes and Metabolism NF-κB nuclear factor-κB RANKL receptor activator of nuclear factor-κB ligand PUGNAc O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenylcarbamate UDP uridine diphosphate Article M-CSF macrophage colony-stimulating factor NF-κB 03 medical and health sciences chemistry.chemical_compound ROS reactive oxygen species 0302 clinical medicine O-GlcNAcylation GalNAc N-acetylgalactosamine Downregulation and upregulation Osteoclast medicine Orthopedics and Sports Medicine chemistry.chemical_classification Reactive oxygen species TRAP tartrate-resistant acid phosphatase biology Activator (genetics) Monocyte Glc glucose GlcNAc N-acetylglucosamine N-acetylglucosamine Cell biology Gal galactose carbohydrates (lipids) 030104 developmental biology medicine.anatomical_structure chemistry Biochemistry RANKL 030220 oncology & carcinogenesis biology.protein Phosphorylation sRANKL soluble receptor activator of nuclear factor-κB ligand lcsh:RC925-935 |
Zdroj: | Bone Reports Bone Reports, Vol 5, Iss, Pp 15-21 (2016) |
ISSN: | 2352-1872 |
DOI: | 10.1016/j.bonr.2016.02.001 |
Popis: | 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), and N-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 of O-GlcNAcylation and showed that GlcNAc increases global O-GlcNAcylation, thereby suppressing the RANKL-dependent phosphorylation of NF-κB p65. Furthermore, an inhibitor of N-acetyl-β-D-glucosaminidase, O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenylcarbamate (PUGNAc), which also increases O-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. A new online only, open access, peer reviewed journal. |
Databáze: | OpenAIRE |
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