RRC ID 63091
著者 Takeuchi T, Horimoto Y, Oyama M, Nakatani S, Kobata K, Tamura M, Arata Y, Hatanaka T.
タイトル Osteoclast Differentiation Is Suppressed by Increased O-GlcNAcylation Due to Thiamet G Treatment.
ジャーナル Biol Pharm Bull
Abstract Osteoclasts are the only bone-resorbing cells in organisms and understanding their differentiation mechanism is crucial for the treatment of osteoporosis. In the present study, we investigated the effect of Thiamet G, an O-GlcNAcase specific inhibitor, on osteoclastogenic differentiation. Thiamet G treatment increased global O-GlcNAcylation in murine RAW264 cells and suppressed receptor activator of nuclear factor-κB ligand (RANKL)-dependent formation in tartrate-resistant acid phosphatase (TRAP)-positive multinuclear cells, thereby suppressing the upregulation of osteoclast specific genes. Meanwhile, knockdown of O-linked N-acetylglucosamine (O-GlcNAc) transferase promoted the formation TRAP-positive multinuclear cells. Thiamet G treatment also suppressed RANKL and macrophage colony-stimulating factor (M-CSF) dependent osteoclast formation and bone-resorbing activity in mouse primary bone marrow cells and human peripheral blood mononuclear cells. These results indicate that the promotion of O-GlcNAc modification specifically suppresses osteoclast formation and its activity and suggest that chemicals affecting O-GlcNAc modification might potentially be useful in the prevention or treatment of osteoporosis in future.
巻・号 43(10)
ページ 1501-1505
公開日 2020-1-1
DOI 10.1248/bpb.b20-00221
PMID 32999159
MeSH Animals Cell Differentiation / drug effects* Cell Differentiation / physiology Female Glycosylation / drug effects Humans Leukocytes, Mononuclear / drug effects Leukocytes, Mononuclear / metabolism Male Mice N-Acetylglucosaminyltransferases / metabolism* Osteoclasts / drug effects* Osteoclasts / metabolism* Pyrans / pharmacology* RAW 264.7 Cells Thiazoles / pharmacology*
IF 1.863
リソース情報
ヒト・動物細胞 RAW 264(RCB0535)