Integrins alpha(6A)beta 1 and alpha(6B)beta 1 promote different stages of chondrogenic cell differentiation.
The differentiation of chondrocytes and of several other cell types is associated with a switch from the alpha(6B) to the alpha(6A) isoform of the laminin alpha(6)beta(1) integrin receptor. To define whether this event plays a functional role in cell differentiation, we used an in vitro model system that allows chick chondrogenic cells to remain undifferentiated when cultured in monolayer and to differentiate into chondrocytes when grown in suspension culture. We report that: (i) upon over-expression of the human alpha(6B), adherent chondrogenic cells differentiate to stage I chondrocytes (i.e. increased type II collagen, reduced type I collagen, fibronectin, alpha(5)beta(1) and growth rate, loss of fibroblast morphology); (ii) the expression of type II collagen requires the activation of p38 MAP kinase; (iii) the over-expression of alpha(6A) induces an incomplete differentiation to stage I chondrocytes, whereas no differentiation was observed in alpha(5) and mock-transfected control cells; (iv) a prevalence of the alpha(6A) subunit is necessary to stabilize the differentiated phenotype when cells are transferred to suspension culture. Altogether, these results indicate a functional role for the alpha(6B) to alpha(6A) switch in chondrocyte differentiation; the former promotes chondrocyte differentiation, and the latter is necessary in stabilizing the differentiated phenotype.
Segat
Daniela
D
Dipartimento di Medicina Sperimentale, Sezione di Anatomia Umana, Universita' di Genova, Italy.
Comai
Riccardo
R
Di Marco
Eddi
E
Strangio
Antonella
A
Cancedda
Ranieri
R
Franzi
Adriano T
AT
Tacchetti
Carlo
C
D000818:Animals; D018929:Cell Culture Techniques / Q000379:methods; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D002642:Chick Embryo; D019902:Chondrocytes / Q000166:cytology* / Q000187:drug effects; D024121:Collagen Type X / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism; D005434:Flow Cytometry; D039121:Integrin alpha6beta1; D016023:Integrins / Q000502:physiology*; D007700:Kinetics; D021122:Protein Subunits
D024121:Collagen Type X; D005353:Fibronectins; D039121:Integrin alpha6beta1; D016023:Integrins; D021122:Protein Subunits