| RRC ID |
63091
|
| Author |
Takeuchi T, Horimoto Y, Oyama M, Nakatani S, Kobata K, Tamura M, Arata Y, Hatanaka T.
|
| Title |
Osteoclast Differentiation Is Suppressed by Increased O-GlcNAcylation Due to Thiamet G Treatment.
|
| Journal |
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.
|
| Volume |
43(10)
|
| Pages |
1501-1505
|
| Published |
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
|
| Resource |
| Human and Animal Cells |
RAW 264(RCB0535) |
