Premium
Expression of Foxo transcription factors during osteoblast differentiation and cell death
Author(s) -
Berry Fred,
Mirzayans Farideh
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.647.8
Subject(s) - microbiology and biotechnology , apoptosis , osteoblast , chondrogenesis , transcription factor , cellular differentiation , chemistry , biology , in vitro , mesenchymal stem cell , gene , biochemistry
Foxo transcription factors regulate the differentiation of adipocytes and myoblasts. However less is known regarding their role in the differentiation of other mesenchyme‐derived cell types such as osteoblasts and chondrocytes. Here we examined the expression levels of Foxo protein and mRNA during osteo‐ and chondrogenesis in vitro. Levels of Foxo1a and Foxo4 protein remained relatively unchanged throughout osteoblast differentiation of MC3T3 cells. Low levels of Foxo3a protein were detected in undifferentiated MC3T3 cells however, Foxo3a increased 1 day after the onset of differentiation. Foxo3a mRNA and protein levels also increased following BMP2 treatment of mouse primary limb bud micromass cultures. Since Foxo proteins play critical roles in mediating cell survival following oxidative stress, we assayed the expression of Foxo proteins following H2O2 treatment. MC3T3 apoptosis was detected by caspase 3 cleavage in cells treated H2O2 and resulted in a decrease in Foxo1a. Finally the affect of modulating Sirt1 activity and Foxo protein function, on survivial of MC3T3‐E1 cells was examined. H2O2‐mediated apoptosis increased in MC3T3‐E1 cells when treated with the Sirt1 agonists, while treatment with Sirt1 inhibitors decreased apoptosis. Together these findings indicate the Foxo3a and Foxo1a participate specific processes governing differentiation and apoptosis of osteoblast cells in vitro.