Calcified Tissue International

, Volume 43, Issue 3, pp 172–178

Effects of the proteinase inhibitors leupeptin and E-64 on osteoclastic bone resorption

  • Vincent Everts
  • Wouter Beertsen
  • Reinier Schröder
Laboratory Investigations

DOI: 10.1007/BF02571316

Cite this article as:
Everts, V., Beertsen, W. & Schröder, R. Calcif Tissue Int (1988) 43: 172. doi:10.1007/BF02571316

Summary

To determine the possible involvement of cysteine-proteinases in bone matrix degradation by osteoclasts, the effects of the proteinase inhibitors leupeptin and E-64 were studied in anin vitro system using mouse bone explants. It was observed that in explants treated with the drugs, the amount of demineralized matrix opposing the ruffled border of the osteoclasts increased about 20-fold within 6 hours. This suggests that demineralization had proceeded whereas matrix degradation had been retarded. It was further noticed that in 12 of 287 osteoclasts, cytoplasmic vacuoles were present containing collagen fibrils that could not be distinguished from those in cartilage or bone. Their intracellular localization was proved by the study of serial sections. Finally, a significant reduction was shown as to the relative surface density of electrontranslucent vacuoles; this would seem to suggest reduced endocytic activity of the cells. Our observations support the view that cysteine-proteinases play an important role in osteoclastic bone resorption. It was further noticed that thein vitro effects of leupeptin and E-64 in certain respects resemble ultrastructural features of pycnodysostosis, an osteopetrosislike bone disorder. The data are in line with the hypothesis that this disease is caused by insufficient activity of osteoclastic cysteine-proteinases.

Key words

Osteoclast Cysteine-proteinases Proteinase inhibitors Collagen phagocytosis 

Copyright information

© Springer-Verlag New York Inc. 1988

Authors and Affiliations

  • Vincent Everts
    • 1
  • Wouter Beertsen
    • 1
  • Reinier Schröder
    • 1
  1. 1.Experimental Oral Biology Group, Laboratory of Histology and Cell Biology, Faculty of Medicine and Department of Periodontology, Academic Centre for Dentistry Amsterdam (ACTA)University of AmsterdamAmsterdamThe Netherlands

Personalised recommendations