In vivo and in vitro comparison of the effects of FGF-2 null and haplo-insufficiency on bone formation in mice

We previously reported that deletion of the Fgf2 gene (Fgf2−/−) resulted in decreased bone mass in adult mice. This study examines the effect of haplo-insuffiency (Fgf2+/−) on bone loss in vertebrae from these mutant mice. Fgf2+/+ mice attained peak bone mass at 8–9 months of age. In contrast BMD was significantly reduced in vertebrae from adult (8–9) Fgf2+/− mice. Exogenous FGF-2 rescued reduced bone nodule formation in Fgf2+/− and Fgf2−/− cultures. Runx2 mRNA was reduced in cultures from Fgf2+/− and Fgf2−/− mice. FGF receptor2 mRNA and protein were markedly reduced in Fgf2+/− and Fgf2−/− mice. Decreased bone formation in Fgf2 mutant mice may correlate with impaired FGFR signaling, decreased Runx2 gene expression.