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Development ePress online publication date 25 Aug 2004
doi: 10.1242/dev.01345

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Research article

Coordination of chondrocyte differentiation and joint formation by {alpha}5{beta}1 integrin in the developing appendicular skeleton


David Garciadiego-Cázares, Carlos Rosales, Masaru Katoh, and Jesús Chimal-Monroy*
* Author for correspondence (e-mail: jchimal{at}servidor.unam.mx)

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 {alpha}5{beta}1 integrin inhibitors and bone morphogenetic protein (BMP) on joint formation. Blocking of {alpha}5{beta}1 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 {alpha}5{beta}1 integrin function still induced the formation of the ectopic joint between proliferating chondrocytes and hypertrophic chondrocytes. By contrast, misexpression of {alpha}5{beta}1 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 {alpha}5{beta}1 integrin on chondrocytes.
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© The Company of Biologists Ltd 2004