TY - JOUR

T1 - Beta1 integrins regulate chondrocyte rotation, G1 progression, and cytokinesis.

AU - Aszodi, Attila

AU - Hunziker, Ernst B

AU - Brakebusch, Cord

AU - Fässler, Reinhard

N1 - Keywords: Animals; Antigens, CD29; Apoptosis; Cartilage; Cell Adhesion; Cell Differentiation; Cell Division; Cell Movement; Cells, Cultured; Chondrocytes; Collagen; Female; G1 Phase; Gene Expression Regulation, Developmental; Genetic Engineering; Male; Mice; Mice, Knockout; Mutation; Osteochondrodysplasias

PY - 2003

Y1 - 2003

N2 - 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.

AB - 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.

U2 - 10.1101/gad.277003

DO - 10.1101/gad.277003

M3 - Journal article

C2 - 14522949

VL - 17

SP - 2465

EP - 2479

JO - Genes & Development

JF - Genes & Development

SN - 0890-9369

IS - 19

ER -