Disruption of the fibroblast growth factor-2 gene results in decreased bone mass and bone formation
Aldemar Montero, Yosuke Okada, Masato Tomita, Masako Ito, Hiroshi Tsurukami, Toshitaka Nakamura, Thomas Doetschman, J. Douglas Coffin, Marja M. Hurley
Aldemar Montero, Yosuke Okada, Masato Tomita, Masako Ito, Hiroshi Tsurukami, Toshitaka Nakamura, Thomas Doetschman, J. Douglas Coffin, Marja M. Hurley
View: Text | PDF
Article

Disruption of the fibroblast growth factor-2 gene results in decreased bone mass and bone formation

Abstract

Basic fibroblast growth factor (FGF-2), an important modulator of cartilage and bone growth and differentiation, is expressed and regulated in osteoblastic cells. To investigate the role of FGF-2 in bone, we examined mice with a disruption of the Fgf2 gene. Measurement of trabecular bone architecture of the femoral metaphysis of Fgf2+/+ and Fgf2–/– adult mice by micro-CT revealed that the platelike trabecular structures were markedly reduced and many of the connecting rods of trabecular bone were lost in the Fgf2–/– mice. Dynamic histomorphometry confirmed a significant decrease in trabecular bone volume, mineral apposition, and bone formation rates. In addition, there was a profound decreased mineralization of bone marrow stromal cultures from Fgf2–/– mice. This study provides strong evidence that FGF-2 helps determine bone mass as well as bone formation.

Authors

Aldemar Montero, Yosuke Okada, Masato Tomita, Masako Ito, Hiroshi Tsurukami, Toshitaka Nakamura, Thomas Doetschman, J. Douglas Coffin, Marja M. Hurley

×

Figure 3

Options: View larger image (or click on image) Download as PowerPoint
(a) Effect of FGF-2 on colony area in mouse bone marrow cultures from Fg...
(a) Effect of FGF-2 on colony area in mouse bone marrow cultures from Fgf2+/+ and Fgf2–/– mice. Cells were plated at a density of 1 million cells per well in αMEM containing penicillin/streptomycin and 10% heat inactivated FCS in the absence or presence of FGF-2 (10 nM). On day 3, media were changed and cells were cultured in differentiation media (αMEM, 10 nM dexamethasone, 10% FCS, 8 mM β-glycerophosphate, 50 μg/mL ascorbic acid) for an additional 11 days. ASignificantly different from control cultures; P < 0.05. BSignificantly different from Fgf2+/+; P < 0.05. (b) Comparison of the ability to form ALP colonies and mineralized nodules as determined by von Kossa staining in mouse bone marrow cultures from Fgf2+/+ and Fgf2–/– mice. Cells were plated at a density of 20 million cells per well in αMEM containing penicillin/streptomycin and 10% heat inactivated FCS. On day 3, media were changed and cells were cultured in differentiation media (αMEM, 10 nM dexamethasone, 10% FCS, 8 mM β-glycerophosphate, 50 μg/mL ascorbic acid) for the indicated times.