TY - JOUR
T1 - Specific inhibitors of vacuolar H+-ATPase trigger apoptotic cell death of osteoclasts
AU - Okahashi, Nobuo
AU - Nakamura, Ichiro
AU - Jimi, Eijiro
AU - Koide, Masanori
AU - Suda, Tatsuo
AU - Nishihara, Tatsuji
PY - 1997/7
Y1 - 1997/7
N2 - 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- 1α 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.
AB - 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- 1α 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.
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U2 - 10.1359/jbmr.1997.12.7.1116
DO - 10.1359/jbmr.1997.12.7.1116
M3 - Article
C2 - 9200012
AN - SCOPUS:0030992507
VL - 12
SP - 1116
EP - 1123
JO - Journal of Bone and Mineral Research
JF - Journal of Bone and Mineral Research
SN - 0884-0431
IS - 7
ER -