Integrins α6Aβ1 and α6Bβ1 Promote Different Stages of Chondrogenic Cell Differentiation

Abstract The differentiation of chondrocytes and of several other cell types is associated with a switch from the α6B to the α6A isoform of the laminin α6β1 integrin receptor. To define whether this event plays a functional role in cell differentiation, we used anin 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 α6B, adherent chondrogenic cells differentiate to stage I chondrocytes (i.e. increased type II collagen, reduced type I collagen, fibronectin, α5β1 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 α6A induces an incomplete differentiation to stage I chondrocytes, whereas no differentiation was observed in α5 and mock-transfected control cells; (iv) a prevalence of the α6A subunit is necessary to stabilize the differentiated phenotype when cells are transferred to suspension culture. Altogether, these results indicate a functional role for the α6B to α6A switch in chondrocyte differentiation; the former promotes chondrocyte differentiation, and the latter is necessary in stabilizing the differentiated phenotype.