Human cystatin C, a cysteine proteinase inhibitor, inhibits bone resorption in vitro stimulated by parathyroid hormone and parathyroid hormone-related peptide of malignancy
Lerner, Ulf H. and Grubb, Anders LU
(1992)
In Journal of Bone and Mineral Research
7(4).
p.433-440
- Abstract
The effect of human recombinant cystatin C, a cysteine proteinase inhibitor, on bone resorption in vitro was evaluated. Bone resorption was assessed by analyzing the release of 45Ca and 3H from mouse calvarial bones prelabeled in vivo by injections with 45Ca or [3H]proline, respectively. In 24 h cultures, cystatin C (50 micrograms/ml) significantly inhibited the release of 45Ca and 3H stimulated by parathyroid hormone (PTH, 15 nmol/liter) or parathyroid hormone-related peptide of malignancy (PTHrP, 15 nmol/liter). The degree of inhibition caused by cystatin C in these 24 h cultures was similar to that caused by calcitonin (30 ng/ml). The inhibitory effect of cystatin C on 45Ca release induced by PTH was sustained in 96 h cultures,... (More)
The effect of human recombinant cystatin C, a cysteine proteinase inhibitor, on bone resorption in vitro was evaluated. Bone resorption was assessed by analyzing the release of 45Ca and 3H from mouse calvarial bones prelabeled in vivo by injections with 45Ca or [3H]proline, respectively. In 24 h cultures, cystatin C (50 micrograms/ml) significantly inhibited the release of 45Ca and 3H stimulated by parathyroid hormone (PTH, 15 nmol/liter) or parathyroid hormone-related peptide of malignancy (PTHrP, 15 nmol/liter). The degree of inhibition caused by cystatin C in these 24 h cultures was similar to that caused by calcitonin (30 ng/ml). The inhibitory effect of cystatin C on 45Ca release induced by PTH was sustained in 96 h cultures, whereas the initial inhibition caused by calcitonin was transient. Cystatin C, 10-100 micrograms/ml, caused a dose-dependent inhibition of PTH (15 nmol/liter), and PTHrP (15 nmol/liter) stimulated 45Ca release. Addition of 50 micrograms/ml of cystatin C to mouse bone cultures inhibited the release of 45Ca induced by PTH and PTHrP at a wide range of submaximal and maximal concentrations of hormones (0.01-10 nmol/liter). No effect of cystatin C on 45Ca release in dead bones could be observed, nor did the inhibitor decrease the release of calcium in control bones. The inhibition by cystatin C on PTH-induced mineral mobilization was reversible. Cystatin C (1-100 micrograms/ml) did not affect protein synthesis or mitotic activities in mouse calvarial bones as assessed by the incorporation of [3H]proline and [3H]thymidine, respectively. These data show that cystatin C is a potent inhibitor of mineral mobilization and matrix degradation in cultured bones stimulated to resorb by PTH and PTHrP and that this effect is not due to general cytotoxicity.
(Less)
- author
- Lerner, Ulf H.
and Grubb, Anders
LU
- publishing date
- 1992
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Bone Resorption/chemically induced, Culture Techniques, Cyclic AMP/analysis, Cystatin C, Cystatins/pharmacology, Cysteine Proteinase Inhibitors/pharmacology, Dactinomycin/pharmacology, Humans, Mitosis/genetics, Molecular Weight, Neoplasm Proteins/pharmacology, Parathyroid Hormone/pharmacology, Parathyroid Hormone-Related Protein, Protein Biosynthesis, Proteins/pharmacology
- in
- Journal of Bone and Mineral Research
- volume
- 7
- issue
- 4
- pages
- 433 - 440
- publisher
- Wiley-Blackwell
- external identifiers
-
- pmid:1319105
- scopus:0026587183
- ISSN
- 0884-0431
- language
- English
- LU publication?
- no
- id
- 34d1066a-5af9-4b3a-b5e3-80209bf29f21
- date added to LUP
- 2021-10-28 10:47:51
- date last changed
- 2024-01-12 02:58:18
@article{34d1066a-5af9-4b3a-b5e3-80209bf29f21,
abstract = {{<p>The effect of human recombinant cystatin C, a cysteine proteinase inhibitor, on bone resorption in vitro was evaluated. Bone resorption was assessed by analyzing the release of 45Ca and 3H from mouse calvarial bones prelabeled in vivo by injections with 45Ca or [3H]proline, respectively. In 24 h cultures, cystatin C (50 micrograms/ml) significantly inhibited the release of 45Ca and 3H stimulated by parathyroid hormone (PTH, 15 nmol/liter) or parathyroid hormone-related peptide of malignancy (PTHrP, 15 nmol/liter). The degree of inhibition caused by cystatin C in these 24 h cultures was similar to that caused by calcitonin (30 ng/ml). The inhibitory effect of cystatin C on 45Ca release induced by PTH was sustained in 96 h cultures, whereas the initial inhibition caused by calcitonin was transient. Cystatin C, 10-100 micrograms/ml, caused a dose-dependent inhibition of PTH (15 nmol/liter), and PTHrP (15 nmol/liter) stimulated 45Ca release. Addition of 50 micrograms/ml of cystatin C to mouse bone cultures inhibited the release of 45Ca induced by PTH and PTHrP at a wide range of submaximal and maximal concentrations of hormones (0.01-10 nmol/liter). No effect of cystatin C on 45Ca release in dead bones could be observed, nor did the inhibitor decrease the release of calcium in control bones. The inhibition by cystatin C on PTH-induced mineral mobilization was reversible. Cystatin C (1-100 micrograms/ml) did not affect protein synthesis or mitotic activities in mouse calvarial bones as assessed by the incorporation of [3H]proline and [3H]thymidine, respectively. These data show that cystatin C is a potent inhibitor of mineral mobilization and matrix degradation in cultured bones stimulated to resorb by PTH and PTHrP and that this effect is not due to general cytotoxicity.</p>}},
author = {{Lerner, Ulf H. and Grubb, Anders}},
issn = {{0884-0431}},
keywords = {{Bone Resorption/chemically induced; Culture Techniques; Cyclic AMP/analysis; Cystatin C; Cystatins/pharmacology; Cysteine Proteinase Inhibitors/pharmacology; Dactinomycin/pharmacology; Humans; Mitosis/genetics; Molecular Weight; Neoplasm Proteins/pharmacology; Parathyroid Hormone/pharmacology; Parathyroid Hormone-Related Protein; Protein Biosynthesis; Proteins/pharmacology}},
language = {{eng}},
number = {{4}},
pages = {{433--440}},
publisher = {{Wiley-Blackwell}},
series = {{Journal of Bone and Mineral Research}},
title = {{Human cystatin C, a cysteine proteinase inhibitor, inhibits bone resorption in vitro stimulated by parathyroid hormone and parathyroid hormone-related peptide of malignancy}},
volume = {{7}},
year = {{1992}},
}