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First published online 25 August 2004
doi: 10.1242/dev.01345
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5ß1 integrin in the developing appendicular skeleton
1 Departamento de Biología Celular y Fisiología, Instituto de
Investigaciones Biomédicas, Universidad Nacional Autónoma de
México, Mexico City, Mexico
2 Departamento de Inmunología, Instituto de Investigaciones
Biomédicas, Universidad Nacional Autónoma de México,
Mexico City, Mexico
3 Genetics and Cell Biology Section, National Cancer Center Research Institute,
Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045, Japan
* Author for correspondence (e-mail: jchimal{at}servidor.unam.mx)
Accepted 9 July 2004
The control point by which chondrocytes take the decision between the
cartilage differentiation program or the joint formation program is unknown.
Here, we have investigated the effect of 
5ß1 integrin inhibitors
and bone morphogenetic protein (BMP) on joint formation. Blocking of
5ß1 integrin by specific antibodies or RGD peptide
(arginine-glycine-aspartic acid) induced inhibition of pre-hypertrophic
chondrocyte differentiation and ectopic joint formation between proliferating
chondrocytes and hypertrophic chondrocytes. Ectopic joint expressed Wnt14,
Gdf5, chordin, autotaxin, type I collagen and CD44, while expression of
Indian hedgehog and type II collagen was downregulated in cartilage.
Expression of these interzone markers confirmed that the new structure is a
new joint being formed. In the presence of BMP7, inhibition of 5ß1
integrin function still induced the formation of the ectopic joint between
proliferating chondrocytes and hypertrophic chondrocytes. By contrast,
misexpression of 5ß1 integrin resulted in fusion of joints and
formation of pre-hypertrophic chondrocytes. These facts indicate that the
decision of which cell fate to make pre-joint or pre-hypertrophic is made on
the basis of the presence or absence of 5ß1 integrin on
chondrocytes.
Key words: Joint formation, Integrin, Hedgehog, BMP, Wnt14, Chondrogenesis, Chondrocyte differentiation, Mouse
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