RRC ID |
39012
|
著者 |
Okahashi N, Nakamura I, Jimi E, Koide M, Suda T, Nishihara T.
|
タイトル |
Specific inhibitors of vacuolar H(+)-ATPase trigger apoptotic cell death of osteoclasts.
|
ジャーナル |
J Bone Miner Res
|
Abstract |
Osteoclasts are multinucleated bone-resorbing cells that play a critical role in bone remodeling. Specific inhibitors of vacuolar H(+)-ATPase (V-ATPase), concanamycin A and bafilomycin A1, abolish bone resorption by osteoclasts. In this study, we examined whether these V-ATPase inhibitors trigger apoptotic cell death in osteoclasts, using murine osteoclast-like multinucleated cells (OCLs) formed in vitro. Acridine orange staining revealed that the treatment of OCLs with concanamycin A resulted in chromatin condensation and alterations in nuclear morphology within a few hours. The TdT-mediated dUTP-nick-end labeling (TUNEL) reaction confirmed the apoptotic features of OCLs treated with concanamycin A. The accelerated apoptotic cell death induced by concanamycin A occurred in OCLs treated with interleukin-1 alpha or macrophage colony-stimulating factor as well, which are known to elongate the survival time of osteoclasts. In contrast, these inhibitors did not induce cell death of osteoblastic cells isolated from mouse calvaria. These results suggest that functional impairment of V-ATPase triggers apoptotic cell death in osteoclasts.
|
巻・号 |
12(7)
|
ページ |
1116-23
|
公開日 |
1997-7-1
|
DOI |
10.1359/jbmr.1997.12.7.1116
|
PMID |
9200012
|
MeSH |
Animals
Anti-Bacterial Agents / pharmacology
Apoptosis / drug effects*
Cells, Cultured
Enzyme Inhibitors / pharmacology*
Interleukin-1 / pharmacology
Kinetics
Macrolides*
Macrophage Colony-Stimulating Factor / pharmacology
Mice
Osteoblasts / cytology
Osteoblasts / drug effects
Osteoblasts / enzymology
Osteoclasts / cytology
Osteoclasts / drug effects*
Osteoclasts / enzymology*
Proton-Translocating ATPases / antagonists & inhibitors*
Vacuolar Proton-Translocating ATPases*
|
IF |
5.854
|
引用数 |
61
|
WOS 分野
|
ENDOCRINOLOGY & METABOLISM
|
リソース情報 |
ヒト・動物細胞 |
MC3T3-E1(RCB1126) |