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Family 2 cystatins inhibit osteoclast-mediated bone resorption in calvarial bone explants

In English

Författare

  • H S Brand
  • U H Lerner
  • Anders Grubb
  • W Beertsen
  • A V N Amerongen
  • V Everts

Summary, in English

Osteoclastic bone resorption depends on the activity of various proteolytic enzymes, in particular those belonging to the group of cysteme protemases. Biochemical studies have shown that cystatins, naturally occurring inhibitors of these enzymes, inhibit bone matrix degradation. Since the mechanism by which cystatins exert this inhibitory effect is not completely resolved yet, we studied the effect of cystatins on bone resorption microscopically and by Ca-release measurements. Calvarial bone explants were cultured in the presence or absence of family 2 cystatins and processed for light and electron microscopic analysis, and the culture media were analyzed for calcium release. Both egg white cystatin and human cystatin C decreased calcium release into the medium significantly. Microscopic analyses of the bone explants demonstrated that in the presence of either inhibitor, a high percentage of osteoclasts was associated with demineralized non-degraded bone matrix. Following a 24-h incubation in the presence of cystatin C, 41% of the cells were adjacent to areas of demineralized non-degraded bone matrix, whereas in controls, this was only 6%. If bone explants were cultured with both PTH and cystatin C, 60% of the osteoclasts were associated with dernineralized non-degraded bone matrix, compared to 27% for bones treated with PTH only (P < 0.01). Our study provides evidence that cystatins, the naturally occurring inhibitors of cysteine protemases, reversibly inhibit bone matrix degradation in the resorption lacunae adjacent to osteoclasts. These findings suggest the involvement of cystatins in the modulation of osteoclastic bone degradation.

Publiceringsår

2004

Språk

Engelska

Sidor

689-696

Publikation/Tidskrift/Serie

Bone

Volym

35

Issue

3

Dokumenttyp

Artikel i tidskrift

Förlag

Elsevier

Ämne

  • Orthopedics

Nyckelord

  • cysteine proteinases
  • cystatins
  • cathepsins
  • bone
  • calcium
  • osteoclasts

Status

Published

ISBN/ISSN/Övrigt

  • ISSN: 1873-2763