Disruption of the fibroblast growth factor 2 (FGF-2) gene results in reduced bone mass in mice and impairs expression of bone morphogenic protein-2 (BMP-2) an important mediator of osteoblast and osteoclast differentiation. Since the relationship between FGF-2 and BMP-2 in bone remodeling has not been fully determined, in this study we examined whether endogenous FGF-2 was necessary for maximal effect of BMP-2 on periosteal bone formation in vivo and bone nodule formation and osteoclast formation in vitro in Fgf2-/- mice. We showed that BMP-2 significantly increased periosteal bone formation by 57% in Fgf2+/+ mice but the changes were not significant in Fgf2-/- littermates. In line with these results we found no significant increase in alkaline phosphatase positive (ALP) activity in calvarial osteoblasts or ALP mineralized colonies in stromal cultures from Fgf2-/- mice after BMP-2 treatment. Moreover, BMP-2 induced osteoclast formation was also impaired in marrow stromal cultures from Fgf2-/- mice. Interestingly, BMP-2 induced nuclear accumulation of the runt related transcription factor (Runx2) was markedly impaired in osteoblasts from Fgf2-/- mice. Examination of the effect of loss of FGF-2 on BMP-2 signaling pathway showed that BMP-2 caused a similar induction of phospho-Smad1/5/8 within 30 min in calvarial osteoblasts from both genotypes. In contrast BMP-2-induced p42/44 MAPK was reduced in Fgf2-/- mice. These findings strongly demonstrated that endogenous FGF-2 is important in the maximal responses of BMP-2 in bone and that this may be dependent on the p42/44 MAPK signaling pathway and downstream modulation of Runx2.

Reduced expression and function of bone morphogenetic protein-2 in bones of Fgf2 null mice

SABBIETI, Maria Giovanna;AGAS, DIMITRIOS;
2008

Abstract

Disruption of the fibroblast growth factor 2 (FGF-2) gene results in reduced bone mass in mice and impairs expression of bone morphogenic protein-2 (BMP-2) an important mediator of osteoblast and osteoclast differentiation. Since the relationship between FGF-2 and BMP-2 in bone remodeling has not been fully determined, in this study we examined whether endogenous FGF-2 was necessary for maximal effect of BMP-2 on periosteal bone formation in vivo and bone nodule formation and osteoclast formation in vitro in Fgf2-/- mice. We showed that BMP-2 significantly increased periosteal bone formation by 57% in Fgf2+/+ mice but the changes were not significant in Fgf2-/- littermates. In line with these results we found no significant increase in alkaline phosphatase positive (ALP) activity in calvarial osteoblasts or ALP mineralized colonies in stromal cultures from Fgf2-/- mice after BMP-2 treatment. Moreover, BMP-2 induced osteoclast formation was also impaired in marrow stromal cultures from Fgf2-/- mice. Interestingly, BMP-2 induced nuclear accumulation of the runt related transcription factor (Runx2) was markedly impaired in osteoblasts from Fgf2-/- mice. Examination of the effect of loss of FGF-2 on BMP-2 signaling pathway showed that BMP-2 caused a similar induction of phospho-Smad1/5/8 within 30 min in calvarial osteoblasts from both genotypes. In contrast BMP-2-induced p42/44 MAPK was reduced in Fgf2-/- mice. These findings strongly demonstrated that endogenous FGF-2 is important in the maximal responses of BMP-2 in bone and that this may be dependent on the p42/44 MAPK signaling pathway and downstream modulation of Runx2.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11581/201296
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