Regulation of osterix (Osx, Sp7) and the Osx promoter by parathyroid hormone in osteoblasts
Bibliographic record
Abstract
Parathyroid hormone (PTH) binds to its receptor on osteoblasts to regulate gene transcription primarily through the elevation of the second messenger cAMP. A number of genes regulated by PTH in osteoblasts contain GC-rich and Sp-binding sites. Osterix (Osx, Sp7) is a transcription factor required for the differentiation of osteoblasts that can bind to Sp-binding sites on gene promoters and regulate their expression. Here, we report the effect of PTH (1-34) on Osx expression in osteoblastic UMR-106-01 cells and murine calvaria. PTH (1-34) and PTH (1-31) inhibited Osx mRNA and protein expression, and this effect could be mimicked by forskolin, 8-bromo-cAMP, or expression of constitutively active Gsalpha (caGsalpha). Treatment of the cells with PTH (3-34) or the EPAC-selective agonist 8CPT-2Me-cAMP had no effect on Osx mRNA, whereas PTH (7-34) or expression of caGqalpha-stimulated Osx mRNA levels. PTH (1-34) treatment did not require new protein synthesis and did not involve changes in Osx mRNA stability. Osx promoter fragments coupled to a luciferase reporter were inhibited by PTH (1-34) treatment in a similar manner to the inhibition of Osx mRNA and protein. Deletion analysis localized PTH inhibition to two regions flanking the Osx1 start site; -304/-119 and -71/+91. These results demonstrate that prolonged exposure to PTH inhibits Osx expression in osteoblasts through sites on its proximal promoter and this suppression occurs through PTH stimulation of cellular cAMP.
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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".