Anti-apoptotic Bcl-2 enhancing requires FGF-2/FGF receptor 1 binding in mouse osteoblasts.
In this study, we investigated the role of prostaglandin F2alpha (PGF2alpha) 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 PGF2alpha 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 PGF2alpha 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 PGF2alpha. Moreover, transmission electron microscopy studies showed that PGF2alpha 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 PGF2alpha induces FGF-2 binding to its specific cell surface receptor 1 leading to a cascade pathway that culminates with increased mouse osteoblast survival.
Agas
Dimitrios
D
Department of Comparative Morphology and Biochemistry, University of Camerino, Camerino (MC), Italy.
Marchetti
Luigi
L
Menghi
Giovanna
G
Materazzi
Stefano
S
Materazzi
Giovanni
G
Capacchietti
Mariolina
M
Hurley
Marja M
MM
Sabbieti
Maria Giovanna
MG
D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002461:Cell Line, Transformed; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D015237:Dinoprost / Q000494:pharmacology; D015536:Down-Regulation; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D019254:Genes, bcl-2; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010006:Osteoblasts / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D034622:RNA Interference; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000378:metabolism*; D012886:Skull / Q000166:cytology; D051028:bcl-2-Associated X Protein / Q000378:metabolism
C494827:Bax protein, mouse; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D016222:Fibroblast Growth Factor 2; D015237:Dinoprost; D051496:Receptor, Fibroblast Growth Factor, Type 1; D053148:Caspase 3; D053453:Caspase 9