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PMID: 14522949 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Beta1 integrins regulate chondrocyte rotation, G1 progression, and cytokinesis.

Genes & development ·Vol. 17 ·No. 19 ·2003-10-01 ·Pages 2465-79

Aszodi A, Hunziker EB, Brakebusch C, Fässler R

Abstract

Beta1 integrins are highly expressed on chondrocytes, where they mediate adhesion to cartilage matrix proteins. To assess the functions of beta1 integrin during skeletogenesis, we inactivated the beta1 integrin gene in chondrocytes. We show here that these mutant mice develop a chondrodysplasia of various severity. beta1-deficient chondrocytes had an abnormal shape and failed to arrange into columns in the growth plate. This is caused by a lack of motility, which is in turn caused by a loss of adhesion to collagen type II, reduced binding to and impaired spreading on fibronectin, and an abnormal F-actin organization. In addition, mutant chondrocytes show decreased proliferation caused by a defect in G1/S transition and cytokinesis. The G1/S defect is, at least partially, caused by overexpression of Fgfr3, nuclear translocation of Stat1/Stat5a, and up-regulation of the cell cycle inhibitors p16 and p21. Altogether these findings establish that beta1-integrin-dependent motility and proliferation of chondrocytes are mandatory events for endochondral bone formation to occur.

MeSH Terms
Animals Apoptosis/genetics Cartilage/pathology,physiology Cell Adhesion/genetics Cell Differentiation/physiology Cell Division/physiology Cell Movement/genetics Cells, Cultured Chondrocytes/cytology,pathology,physiology Collagen/metabolism,ultrastructure Female G1 Phase/physiology Gene Expression Regulation, Developmental Genetic Engineering/methods Integrin beta1/physiology Male Mice Mice, Knockout Mutation Osteochondrodysplasias/genetics,physiopathology
Chemicals
Integrin beta1 Collagen
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Aszodi Attila
Max Planck Institute for Biochemistry, Department for Molecular Medicine, 82152 Martinsried, Germany.
Hunziker Ernst B
Brakebusch Cord
Fässler Reinhard
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.277003
Published
2003-10-01
Pages
2465-79
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC218082
Subset
IM
External Links
PubMed source DOI: 10.1101/gad.277003 PMC Full Text View journal details
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