In this study, we investigated the role of prostaglandin F2α (PGF2α) in mouse osteoblast survival and the function of fibroblast growth factor 2 (FGF-2) and fibroblast growth factor receptor 1 (FGFR1) in this process. In particular, for the first time, we demonstrated that PGF2α increased osteoblast survival in a dose-dependent manner and we showed that the effect is correlated with an increase in Bcl-2/Bax ratio. Furthermore, we demonstrated that PGF2α caused a decrement of the active caspases 9 and 3. By blocking FGF-2 with the specific neutralizing antibody and by depletion of FGFR1 gene with a specific siRNA, we showed that FGFR1 and FGF-2 are critical for the increment of Bcl-2/Bax ratio and the decrement of the active caspases 9 and 3, induced by PGF2α. Moreover, transmission electron microscopy studies showed that PGF2α increased binding of FGF-2 and FGFR1 and co-localization of reactive sites at plasma membrane level. In conclusion, we report a novel mechanism in which PGF2α induces FGF-2 binding to its specific cell surface receptor 1 leading to a cascade pathway that culminates with increased mouse osteoblast survival.
Antiapoptotic Bcl-2 enhancing requires FGF-2/FGF receptor-1 binding in mouse osteoblasts
AGAS, DIMITRIOS;MARCHETTI, Luigi;SABBIETI, Maria Giovanna
2008-01-01
Abstract
In this study, we investigated the role of prostaglandin F2α (PGF2α) in mouse osteoblast survival and the function of fibroblast growth factor 2 (FGF-2) and fibroblast growth factor receptor 1 (FGFR1) in this process. In particular, for the first time, we demonstrated that PGF2α increased osteoblast survival in a dose-dependent manner and we showed that the effect is correlated with an increase in Bcl-2/Bax ratio. Furthermore, we demonstrated that PGF2α caused a decrement of the active caspases 9 and 3. By blocking FGF-2 with the specific neutralizing antibody and by depletion of FGFR1 gene with a specific siRNA, we showed that FGFR1 and FGF-2 are critical for the increment of Bcl-2/Bax ratio and the decrement of the active caspases 9 and 3, induced by PGF2α. Moreover, transmission electron microscopy studies showed that PGF2α increased binding of FGF-2 and FGFR1 and co-localization of reactive sites at plasma membrane level. In conclusion, we report a novel mechanism in which PGF2α induces FGF-2 binding to its specific cell surface receptor 1 leading to a cascade pathway that culminates with increased mouse osteoblast survival.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
