β1 integrins regulate chondrocyte rotation, G1 progression, and cytokinesis

Genes and Development - Tập 17 Số 19 - Trang 2465-2479 - 2003
Attila Aszódi1, Ernst B. Hunziker2, Cord Brakebusch3, Reinhard Fässler1
1Fässler, Reinhard / Molecular Medicine, Max Planck Institute of Biochemistry, Max Planck Society
2ITI Research Institute for Dental and Skeletal Biology, University of Bern, 3010 Bern, Switzerland
3Former Research Groups, Max Planck Institute of Biochemistry, Max Planck Society

Tóm tắt

β1 integrins are highly expressed on chondrocytes, where they mediate adhesion to cartilage matrix proteins. To assess the functions of β1 integrin during skeletogenesis, we inactivated the β1 integrin gene in chondrocytes. We show here that these mutant mice develop a chondrodysplasia of various severity. β1-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 β1-integrin-dependent motility and proliferation of chondrocytes are mandatory events for endochondral bone formation to occur.

Từ khóa


Tài liệu tham khảo

10.1083/jcb.143.5.1399

1999, Mol. Cell. Biol., 19, 7841, 10.1128/MCB.19.11.7841

10.1016/S0945-053X(99)00009-8

10.1177/002215549904701102

10.1161/hh1501.094874

10.1093/emboj/cdg245

10.1093/emboj/19.15.3990

10.1172/JCI200215468

10.1128/MCB.22.18.6627-6635.2002

10.1016/S0945-053X(99)00027-X

10.1083/jcb.147.5.1109

1986, J. Microsc., 143, 47, 10.1111/j.1365-2818.1986.tb02765.x

10.1002/ar.1090460409

10.1101/gad.9.15.1896

10.1083/jcb.128.5.979

10.1083/jcb.79.1.268

10.1126/science.285.5430.1028

10.1038/sj.embor.embor801

10.1006/dbio.2001.0336

1987, J. Microsc., 147, 229, 10.1111/j.1365-2818.1987.tb02837.x

10.1016/0092-8674(82)90221-5

10.1002/(SICI)1097-0177(199711)210:3<249::AID-AJA6>3.0.CO;2-G

1987, J. Bone Joint Surg. Am., 69, 162, 10.2106/00004623-198769020-00002

10.1016/S0092-8674(02)00971-6

10.1016/S1534-5807(02)00157-0

1996, Science, 273, 663, 10.1126/science.273.5275.663

10.1093/hmg/8.1.35

2000, Biorheology, 37, 109

2001, Development, 128, 5099, 10.1242/dev.128.24.5099

1999, Blood, 93, 165, 10.1182/blood.V93.1.165

2002, Genes & Dev., 17, 926

10.1038/sj.onc.1203877

2001, Development, 128, 1481, 10.1242/dev.128.9.1481

10.1016/S1074-7613(00)80216-2

10.1016/S0945-053X(00)00122-0

10.1038/85471

10.1083/jcb.113.2.321

10.1006/excr.1998.3933

1999, Genes & Dev., 13, 2072, 10.1101/gad.13.16.2072

10.1038/386288a0

10.1074/jbc.M206286200

2001, Osteoarth. Cart., 9, S109

1996, Science, 273, 613, 10.1126/science.273.5275.613

10.1006/excr.1997.3692

Thông tin
Thông tin xuất bản

Genes and Development

Tập 17 Số 19

2465-2479

Thông tin tác giả