Document Detail


Targeted deletion of Capn4 in cells of the chondrocyte lineage impairs chondrocyte proliferation and differentiation.
MedLine Citation:
PMID:  20368361     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Calpains are calcium-dependent intracellular cysteine proteases, which include ubiquitously expressed mu- and m-calpains. Both calpains are heterodimers consisting of a large catalytic subunit and a small regulatory subunit. The calpain small subunit encoded by the gene Capn4 directly binds to the intracellular C-terminal tail of the receptor for the parathyroid hormone (PTH) and PTH-related peptide and modulates cellular functions in cells of the osteoblast lineage in vitro and in vivo. To investigate a physiological role of the calpain small subunit in cells of the chondrocyte lineage, we generated chondrocyte-specific Capn4 knockout mice. Mutant embryos had reduced chondrocyte proliferation and differentiation in embryonic growth plates compared with control littermates. In vitro analysis further revealed that deletion of Capn4 in cells of the chondrocyte lineage correlated with impaired cell cycle progression at the G(1)/S transition, reduced cyclin D gene transcription, and accumulated cell cycle proteins known as calpain substrates. Moreover, silencing of p27(Kip1) rescued an impaired cell growth phenotype in Capn4 knockdown cells, and reintroducing the calpain small subunit partially normalized cell growth and accumulated cyclin D protein levels in a dose-dependent manner. Collectively, our findings suggest that the calpain small subunit is essential for proper chondrocyte functions in embryonic growth plates.
Authors:
Aki Kashiwagi; Ernestina Schipani; Mikaela J Fein; Peter A Greer; Masako Shimada
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-04-05
Journal Detail:
Title:  Molecular and cellular biology     Volume:  30     ISSN:  1098-5549     ISO Abbreviation:  Mol. Cell. Biol.     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-05-12     Completed Date:  2010-06-01     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  8109087     Medline TA:  Mol Cell Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2799-810     Citation Subset:  IM    
Affiliation:
50 Blossom Street, Thier 10, Boston, MA 02114, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Biological Markers / metabolism
Calpain / genetics*,  metabolism
Cell Cycle / physiology
Cell Differentiation / physiology*
Cell Lineage*
Cell Proliferation*
Cells, Cultured
Chondrocytes / cytology,  physiology*
Cyclin D1 / genetics,  metabolism
Cyclin-Dependent Kinase Inhibitor p27 / genetics,  metabolism
Embryo, Mammalian / cytology,  metabolism
Female
Gene Deletion*
Growth Plate / cytology,  physiology
Mice
Mice, Knockout
Parathyroid Hormone / genetics,  metabolism
Parathyroid Hormone-Related Protein / genetics,  metabolism
Pregnancy
Protein Isoforms / genetics,  metabolism
Protein Subunits / genetics,  metabolism
Transforming Growth Factor beta / genetics
Grant Support
ID/Acronym/Agency:
MOP-81189//Canadian Institutes of Health Research; R01 DK072102/DK/NIDDK NIH HHS; R01 DK072102/DK/NIDDK NIH HHS; R01 DK072102-03/DK/NIDDK NIH HHS; R01 DK072102-04/DK/NIDDK NIH HHS; R01 DK072102-05S1/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Biological Markers; 0/Cdkn1b protein, mouse; 0/Parathyroid Hormone; 0/Parathyroid Hormone-Related Protein; 0/Protein Isoforms; 0/Protein Subunits; 0/Transforming Growth Factor beta; 136601-57-5/Cyclin D1; 147604-94-2/Cyclin-Dependent Kinase Inhibitor p27; EC 3.4.22.-/Calpain; EC 3.4.22.-/Capns1 protein, mouse
Comments/Corrections

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