| TI:
|
Title
Calpain Is Required for Normal Osteoclast Function
and Is Down-regulated by Calcitonin |
| AU:
|
Author
Marzia, Marilena; Chiusaroli, Riccardo; Neff,
Lynn; Kim, Na-Young; Chishti, Athar H; Baron,
Roland; Horne, William C |
| AF:
|
Author Affiliation
Departments of Orthopaedics and Rehabilitation and
Cell Biology, Yale University School of Medicine,
New Haven, Connecticut 06520-8044, the Department
of Medicine, St. Elizabeth's Medical Center, Tufts
University School of Medicine, Boston,
Massachusetts 02135, and the Department of
Pharmacology/Cancer Center, University of Illinois
College of Medicine, Chicago, Illinois 60607
|
| SO:
|
Source
Journal of Biological Chemistry [J. Biol. Chem.].
Vol. 281, no. 14, pp. 9745-9754. 7 Apr 2006
|
| IS:
|
ISSN
0021-9258 |
| EI:
|
Electronic ISSN
1083-351X |
| DE:
|
Descriptors
Osteoclasts; Calpain; Calcitonin; Motility; Bone
resorption; Tibia |
| AB:
|
Abstract
Osteoclast motility is thought to depend on rapid
podosome assembly and disassembly. Both mu -calpain
and m-calpain, which promote the formation and
disassembly of focal adhesions, were observed in
the podosome belt of osteoclasts. Calpain
inhibitors disrupted the podosome belt, blocked
the constitutive cleavage of the calpain
substrates filamin A, talin, and Pyk2, which are
enriched in the podosome belt, induced osteoclast
retraction, and reduced osteoclast motility and
bone resorption. The motility and resorbing
activity of mu -calpain super(-/-) osteoclast-like
cells were also reduced, indicating that mu -calpain
is required for normal osteoclast activity.
Histomorphometric analysis of tibias from mu -calpain
super(-/-) mice revealed increased osteoclast
numbers and decreased trabecular bone volume that
was apparent at 10 weeks but not at 5 weeks of
age. In vitro studies suggested that the increased
osteoclast number in the mu -calpain super(-/-)
bones resulted from increased osteoclast survival,
not increased osteoclast formation. Calcitonin
disrupted the podosome ring, induced osteoclast
retraction, and reduced osteoclast motility and
bone resorption in a manner similar to the effects
of calpain inhibitors and had no further effect on
these parameters when added to osteoclasts
pretreated with calpain inhibitors. Calcitonin
inhibited the constitutive cleavage of a
fluorogenic calpain substrate and transiently
blocked the constitutive cleavage of filamin A,
talin, and Pyk2 by a protein kinase C-dependent
mechanism, demonstrating that calcitonin induces
the inhibition of calpain in osteoclasts. These
results indicate that calpain activity is required
for normal osteoclast activity and suggest that
calcitonin inhibits osteoclast bone resorbing
activity in part by down-regulating calpain
activity. |
| LA:
|
Language
English |
| SL:
|
Summary Language
English |
| PY:
|
Publication Year
2006 |
| PT:
|
Publication Type
Journal Article |
| PB:
|
Publisher
American Society for Biochemistry and Molecular
Biology, 9650 Rockville Pike Bethesda MD
20814-3996 USA |
| CL:
|
Classification
T 20029 Enzymes |
| UD:
|
Update
200604 |
| SF:
|
Subfile
Calcium & Calcified Tissue Abstracts |
| AN:
|
Accession Number
6747883 |
| PG:
|
Journal Pages
9745-9754 |
| JV:
|
Journal Volume
281 |
| JI:
|
Journal Issue
14 |
