Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10765412 | Biochemical and Biophysical Research Communications | 2010 | 5 Pages |
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 Fgf2â/â BMSCs. We found that FGF2 stimulated ATF4 mRNA expression as early as 20Â min and increased ATF4 protein expression after three hours of treatment. BMSCs from Fgf2+/+ and Fgf2â/â 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 Fgf2â/â 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 Fgf2â/â BMSCs. These results suggest that impaired bone mass and bone formation in Fgf2 null mice may be due in part to reduced ATF4 expression.
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Authors
Yurong Fei, Liping Xiao, Marja M. Hurley,