A variety of pathologies such as skeletal fracture,
neoplasia and
inflammation compromise tissue perfusion and thereby decrease tissue
oxygen tension. We and others have demonstrated that
hypoxia is a potent stimulant for MSC (mesenchymal stem cell) recruitment and differentiation, yet to date little research has focused on the effects of
oxygen tension on MSC migration. In the present study, we examined the effects of
hypoxia and the potential role of the
GTPase RhoA and HIF-1α (
hypoxia-inducible factor 1α) on MSC migration. Our results demonstrate that
hypoxia decreases MSC migration through an HIF-1α and RhoA-mediated pathway. The active
GTP-bound form of RhoA was reduced in 1%
oxygen, whereas activation of RhoA under hypoxic conditions rescued migration. Furthermore, stabilization of HIF-1α under normoxic conditions attenuated cell migration similar to that of
hypoxia. These results suggest that
hypoxia negatively affects MSC migration by regulating activation of
GTPases. These results highlight the importance of
oxygen in regulating the recruitment of progenitor cells to areas of ischaemic tissue damage.