| Targeted deletion of Capn4 in cells of the chondrocyte lineage impairs chondrocyte proliferation and differentiation. | |
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MedLine Citation:
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PMID: 20368361 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Aki Kashiwagi; Ernestina Schipani; Mikaela J Fein; Peter A Greer; Masako Shimada |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-04-05 |
Journal Detail:
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Title: Molecular and cellular biology Volume: 30 ISSN: 1098-5549 ISO Abbreviation: Mol. Cell. Biol. Publication Date: 2010 Jun |
Date Detail:
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Created Date: 2010-05-12 Completed Date: 2010-06-01 Revised Date: 2012-12-26 |
Medline Journal Info:
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Nlm Unique ID: 8109087 Medline TA: Mol Cell Biol Country: United States |
Other Details:
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Languages: eng Pagination: 2799-810 Citation Subset: IM |
Affiliation:
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50 Blossom Street, Thier 10, Boston, MA 02114, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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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:
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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:
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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 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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