Parathyroid Hormone-Induced Up-Regulation of Connexin-43 Messenger Ribonucleic Acid (mRNA) Is Mediated by Sequences within Both the Promoter and the 3′Untranslated Region of the mRNA**This work was supported in part by the group Grant GR-13299 from the Medical Research Council. The Natural Science and Engineering Research Council of Canada provided research stipend funding for this work.
Bibliographic record
Abstract
The gap junction protein connexin 43 (Cx43) mediates communication between osteoblasts and is important for maximal PTH responsiveness. We examined the role of the Cx43 promoter and messenger RNA 3' untranslated region (UTR) in conferring responsiveness to PTH in the rat osteosarcoma cell line UMR-106. PTH induced a 4-fold increase in luciferase activity of a reporter construct containing 1.6 kb 5' of the transcription start site. Deletion analysis of the promoter localized responsive sequences to between -31 to +1 bp. PTH treatment of transgenic mice containing the 1.6 kb promoter luciferase construct induced increases in luciferase and Cx43 immunoreactivity in bone cells underlying the tibial growth plate. The full Cx43 3'UTR conferred a 3-fold response to PTH when placed 3' of a CMV-luciferase construct. Deletion analysis localized responsive sequences to between 2510 and 3132 of the 3'UTR. Cloning of this segment 5' of the CMV promoter disrupted the PTH response, indicating this sequence does not function as an enhancer. Sequences within the promoter conferred responsiveness to forskolin, whereas the 3'UTR responded to both TPA and forskolin. These data indicate that PTH responsive sequences are present in the Cx43 promoter and 3'UTR, suggesting that transcriptional and posttranscriptional pathways operate to regulate PTH-induced Cx43 expression in osteoblast cells.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| 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) | 0.002 | 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 source (direct Gemma or distilled Codex), 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".