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, asbmb@asbmb.faseb.org, http://www.jbc.org

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