Specific inhibitors of vacuolar H+-ATPase trigger apoptotic cell death of osteoclasts

Nobuo Okahashi, Ichiro Nakamura, Eijiro Jimi, Masanori Koide, Tatsuo Suda, Tatsuji Nishihara

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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- 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.

Original languageEnglish
Pages (from-to)1116-1123
Number of pages8
JournalJournal of Bone and Mineral Research
Volume12
Issue number7
DOIs
Publication statusPublished - Jan 1 1997
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine

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