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

Brand, H S; Lerner, U H; Grubb, Anders LU ; Beertsen, W; Amerongen, A V N and Everts, V (2004) In Bone 35(3). p.689-696
Abstract
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
cysteine proteinases, cystatins, cathepsins, bone, calcium, osteoclasts
in
Bone
volume
35
issue
3
pages
689 - 696
publisher
Elsevier
external identifiers
  • wos:000224076600016
  • pmid:15336605
  • scopus:4344707661
ISSN
1873-2763
DOI
10.1016/j.bone.2004.05.015
language
English
LU publication?
yes
id
c20fcced-a2e1-4e83-b18c-737e25177189 (old id 266572)
date added to LUP
2007-10-17 11:33:41
date last changed
2017-05-21 04:18:09
@article{c20fcced-a2e1-4e83-b18c-737e25177189,
  abstract     = {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 &lt; 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.},
  author       = {Brand, H S and Lerner, U H and Grubb, Anders and Beertsen, W and Amerongen, A V N and Everts, V},
  issn         = {1873-2763},
  keyword      = {cysteine proteinases,cystatins,cathepsins,bone,calcium,osteoclasts},
  language     = {eng},
  number       = {3},
  pages        = {689--696},
  publisher    = {Elsevier},
  series       = {Bone},
  title        = {Family 2 cystatins inhibit osteoclast-mediated bone resorption in calvarial bone explants},
  url          = {http://dx.doi.org/10.1016/j.bone.2004.05.015},
  volume       = {35},
  year         = {2004},
}