The regulation of proliferation and differentiation in oligodendrocyte progenitor cells by αv integrins

We have previously shown that oligodendrocyte progenitor cells exhibit developmental switching between αv-associated β integrin subunits to sequentially express αvβ1, αvβ3 and αvβ5 integrins during differentiation in vitro. To understand the role that αvβ3 integrin may play in regulating oligodendrocyte progenitor cell behaviour, cells of the rat cell line, CG-4, were genetically engineered to constitutively express αvβ3 integrin by transfection with full-length human β3 integrin subunit cDNA. Time-lapse videomicroscopy showed no effect of β3 expression on cell migration but revealed enhanced proliferation on vitronectin substrata. Comparison of mitotic indices, as measured by 5-bromo-2'-deoxyuridine incorporation, confirmed that human β3 integrin-expressing cells exhibited enhanced proliferation, as compared to both vector-only transfected, and wild-type CG-4 cells when switched to differentiation medium from growth medium, but only in cultures grown on vitronectin and not on poly-D-lysine. The effects on proliferation were inhibited by a function-blocking antibody specifically directed against the human β3 integrin subunit. Human β3 integrin-expressing cells also exhibited reduced differentiation. This differentiation could be reduced still further by a function-blocking monoclonal antibody against αvβ5 integrin, as could differentiation in the wild-type CG-4 cells. Taken together, these results suggest that αvβ3 integrin may regulate oligodendroglial cell proliferation and that both downregulation of αvβ3 integrin expression and signalling through αvβ5 integrin may be critical to continued differentiation in vitro.