title: Glucosamine Suppresses Osteoclast Differentiation through the Modulation of Glycosylation Including O-GlcNAcylation.
abstract: Osteoclasts represent the only bone resorbing cells in an organism. In this study, we investigated the effect of glucosamine (GlcN), a nutrient used to prevent joint pain and bone loss, on the osteoclastogenesis of murine macrophage-like RAW264 cells. GlcN supplementation suppressed the upregulation of osteoclast-specific genes (tartrate-resistant acid phosphatase (TRAP), cathepsin K, matrix metallopeptidase 9, and nuclear factor of activated T cell c1 (NFATc1)), receptor activator of nuclear factor-κB ligand (RANKL)-dependent upregulation of TRAP enzyme activity, and the formation of TRAP-positive multinuclear cells more effectively than N-acetylglucosamine (GlcNAc), which we have previously shown to inhibit osteoclast differentiation. To clarify the mechanism by which GlcN suppresses osteoclastogenesis, we further investigated the effect of GlcN on O-GlcNAcylation by Western blotting and on other types of glycosylation by lectin blotting. We found that, upon addition of GlcN, the O-GlcNAcylation of cellular proteins was increased whereas α2,6-linked sialic acid modification was decreased. Therefore, these glycan modifications in cellular proteins may contribute to the suppression of osteoclastogenesis.
authors.affiliation: Faculty of Pharmaceutical Sciences, Josai University.
authors.forename: Tomoharu
authors.initials: T
authors.lastname: Takeuchi
authors.forename: Aya
authors.initials: A
authors.lastname: Sugimoto
authors.forename: Nao
authors.initials: N
authors.lastname: Imazato
authors.forename: Mayumi
authors.initials: M
authors.lastname: Tamura
authors.forename: Sachie
authors.initials: S
authors.lastname: Nakatani
authors.forename: Kenji
authors.initials: K
authors.lastname: Kobata
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Arata
mesh_terms: D000215:Acylation; D000818:Animals; D001862:Bone Resorption / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D005944:Glucosamine / Q000494:pharmacology*; D006031:Glycosylation; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D010010:Osteoclasts / Q000187:drug effects* / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects*; D011499:Protein Processing, Post-Translational / Q000187:drug effects*; D053245:RANK Ligand / Q000378:metabolism; D000071681:Tartrate-Resistant Acid Phosphatase / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D053245:RANK Ligand; D000071681:Tartrate-Resistant Acid Phosphatase; D005944:Glucosamine