Expression of Foxo transcription factors during osteoblast differentiation and cell death
Bibliographic record
Abstract
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.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".