Expression of vacuolar H+-ATPase in osteoclasts and its role in resorption

Takahisa Sasaki, Mei Hua Hong, Nobuyuki Udagawa, Yoshinori Moriyama

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

By means of light- and electron-microscopic immunocytochemistry, we have demonstrated the expression of vacuolar H+-ATPase in mouse osteoclasts. In fully differentiated osteoclasts, intense immunolabeling was observed along the plasma membranes including those of ruffled borders and associated pale vesicles and vacuoles, whereas those of clear zones and basolateral cell surfaces were entirely free of immunoreaction. Specific expression of vacuolar H+-ATPase was also detected over polyribosomes and cisterns of the rough-surfaced endoplasmic reticulum. Multinucleated osteoclastic cells were suspended on dentine slices and cultured for 48 h in the presence or absence of either concanamycin B or bafilomycin A1, specific inhibitors of vacuolar H+-ATPase. Morphometric analysis of co-cultured dentine slices with backscattered electron microscopy revealed that both inhibitors strongly reduced the formation of resorption lacunae in a dose-dependent manner. These results suggest that vacuolar H+-ATPase is produced in the rough-surfaced endoplasmic reticulum, stored in the membrane vesicles, and transported into the ruffled border membranes of osteoclasts, and that this enzyme plays a key role in the creation of an acidic subosteoclastic microenvironment for the demineralization of co-cultered substrates.

Original languageEnglish
Pages (from-to)265-271
Number of pages7
JournalCell and Tissue Research
Volume278
Issue number2
DOIs
Publication statusPublished - Nov 1 1994

Keywords

  • Bone resorption
  • Immuno-electron microscopy
  • Mouse (ddY)
  • Osteoclast
  • Vacuolar H-ATPase

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology
  • Cell Biology

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