Beta1 integrin deficiency results in multiple abnormalities of the knee joint

The lack of beta1 integrins on chondrocytes leads to severe chondrodysplasia associated with high mortality rate around birth. To assess the impact of beta1 integrin-mediated cell-matrix interactions on the function of adult knee joints, we conditionally deleted the beta1 integrin gene in early limb...

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Bibliographic Details
Published in:The Journal of biological chemistry 2009-08, Vol.284 (35), p.23780-23792
Main Authors: Raducanu, Aurelia, Hunziker, Ernst B, Drosse, Inga, Aszódi, Attila
Format: Article
Language:English
Subjects:
Animals
Cartilage, Articular - abnormalities
Cartilage, Articular - cytology
Cartilage, Articular - metabolism
Cell Differentiation
Cell Proliferation
Chondrocytes - cytology
Chondrocytes - metabolism
Female
Gene Silencing
Integrin beta1 - genetics
Integrin beta1 - metabolism
Knee Joint - abnormalities
Knee Joint - cytology
Knee Joint - metabolism
Male
Mice
Mice, Knockout
Signal Transduction
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Summary:The lack of beta1 integrins on chondrocytes leads to severe chondrodysplasia associated with high mortality rate around birth. To assess the impact of beta1 integrin-mediated cell-matrix interactions on the function of adult knee joints, we conditionally deleted the beta1 integrin gene in early limb mesenchyme using the Prx1-cre transgene. Mutant mice developed short limbed dwarfism and had joint defects due to beta1 integrin deficiency in articular regions. The articular cartilage (AC) was structurally disorganized, accompanied by accelerated terminal differentiation, altered shape, and disrupted actin cytoskeleton of the chondrocytes. Defects in chondrocyte proliferation, cytokinesis, and survival resulted in hypocellularity. However, no significant differences in cartilage erosion, in the expression of matrix-degrading proteases, or in the exposure of aggrecan and collagen II cleavage neoepitopes were observed between control and mutant AC. We found no evidence for disturbed activation of MAPKs (ERK1/2, p38, and JNK) in vivo. Furthermore, fibronectin fragment-stimulated ERK activation and MMP-13 expression were indistinguishable in control and mutant femoral head explants. The mutant synovium was hyperplastic and frequently underwent chondrogenic differentiation. beta1-null synoviocytes showed increased proliferation and phospho-focal adhesion kinase expression. Taken together, deletion of beta1 integrins in the limb bud results in multiple abnormalities of the knee joints; however, it does not accelerate AC destruction, perturb cartilage metabolism, or influence intracellular MAPK signaling pathways.
ISSN:0021-9258
DOI:10.1074/jbc.M109.039347