Effect of zoledronate, a third-generation bisphosphonate, on proliferation and apoptosis of human dental pulp stem cells
Bibliographic record
Abstract
Clinical use of zoledronate is accompanied by osteonecrosis of the jaw but the pathogenesis is not well understood. We assumed that zoledronate may have cytotoxicity against stem cells of the oral cavity and in this way helps to initiate or promote osteonecrosis. Dental pulp stem cells (DPSCs) and gingival fibroblasts (GFs) were isolated from volunteers who were undergoing a third molar extraction. The proliferation of DPSCs and GFs was evaluated using the thiazolyl blue tetrazolium bromide assay. The effect of zoledronate on apoptosis was determined by propidium iodide staining and Western blotting analysis. Incubation with zoledronate for 72 h and 7 days significantly decreased proliferation of DPSCs and GFs at concentrations of more than 0.4 μmol/L (p < 0.001). The IC50 of zoledronate was lower for DPSCs than for GFs (0.92 versus 3.5 μmol/L for 7 days of treatment). After 72 h of treatment with zoledronate, the percentage of apoptotic DPSCs significantly increased, which was accompanied by an increased level of pro-apoptotic proteins caspase-3 and Bax and decreased the level of the anti-apoptotic protein Bcl-2. In conclusion, zoledronate has anti-proliferative and pro-apoptotic effects in DPSCs. These effects may be involved in promoting zoledronate-induced osteonecrosis and suggest an unfavorable impact of this drug on regenerative potentials of the body stem 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) | 0.001 | 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".