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Fibroblast growth factor 2 positively regulates expression of activating transcription factor 4 in osteoblasts.

Abstract：

:Our previous studies showed that basic fibroblast growth factor 2 (FGF2) null mice display markedly reduced bone mass and bone formation. However, the mechanism by which FGF2 regulates bone mass or bone formation is not fully defined. Activating transcription factor 4 (ATF4), one member of activating transcription factor/cAMP response element binding family, is a transcription factor required for osteoblast terminal differentiation. Here we investigate the ability of FGF2 to increase expression of ATF4 in bone marrow stromal cells (BMSCs) and examine ATF4 expression in Fgf2(-/-) BMSCs. We found that FGF2 stimulated ATF4 mRNA expression as early as 20 min and increased ATF4 protein expression after three hours of treatment. BMSCs from Fgf2(+/+) and Fgf2(-/-) mice were cultured in osteogenesis medium. We observed reduced alkaline phosphatase staining, decreased mineralized nodules and reduced osteocalcin expression, and reduced expression of ATF4 in Fgf2(-/-) BMSC cultures compared to Fgf2(+/+) BMSCs. This study is the first demonstration that ATF4 expression can be stimulated by FGF2 in osteoblasts and that ATF4 expression is significantly reduced in differentiated Fgf2(-/-) BMSCs. These results suggest that impaired bone mass and bone formation in Fgf2 null mice may be due in part to reduced ATF4 expression.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Fei Y,Xiao L,Hurley MM

doi

10.1016/j.bbrc.2009.11.059

subject

Has Abstract

pub_date

2010-01-01 00:00:00

pages

335-9

issue

1

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(09)02234-7

journal_volume

391

pub_type

杂志文章

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