N-acetylglucosamine suppresses osteoclastogenesis in part through the promotion of O-GlcNAcylation

Autor: Tomoharu Takeuchi, Moyuko Nagasaka, Mayumi Tamura, Yoichiro Arata, Miyuki Shimizu
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.
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Databáze: OpenAIRE