Apical Papilla Regulates Dental Follicle Fate via the OGN-Hh Pathway
Bibliographic record
Abstract
Root apical complex, including Hertwig’s epithelial root sheath, apical papilla, and dental follicle (DF), is the germinal center of root development, wherein the DF constantly develops into periodontal tissue. However, whether DF development is regulated by the adjacent apical papilla remains largely unknown. In this study, we employed a transwell coculture system and found that stem cells from the apical papilla (SCAPs) inhibit the differentiation and maintain the stemness of dental follicle stem cells (DFSCs). Meanwhile, partial SCAP differentiation markers were upregulated after DFSC coculture. High-throughput RNA sequencing revealed that the Hedgehog (Hh) pathway was significantly downregulated in DFSCs cocultured with SCAPs. Upregulation or downregulation of the Hh pathway can respectively activate or inhibit the multidirectional differentiation of DFSCs. Osteoglycin (OGN) (previously known as mimecan) is highly expressed in the dental papilla, similarly to Hh pathway factors. By secreting OGN, SCAP regulated the stemness and multidirectional differentiation of DFSCs via the OGN-Hh pathway. Finally, <i>Ogn</i><sup>–/–</sup> mice were established using the CRISPR/Cas9 system. We found that the root length growth rate was accelerated during root development from PN0 to PN30 in <i>Ogn</i><sup>–/–</sup> mice. Moreover, the hard tissues (including dentin and cementum) of the root in <i>Ogn</i><sup>–/–</sup> mice were thicker than those in wild-type mice. These phenotypes were likely due to Hh pathway activation and the increased cell proliferation and differentiation in both the apical papilla and DF. The current work elucidates the molecular regulation of early periodontal tissue development, providing a theoretical basis for future research on tooth root biology and periodontal tissue regeneration.
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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 | 0.003 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.006 | 0.005 |
| Research integrity | 0.000 | 0.002 |
| Insufficient payload (model declined to judge) | 0.282 | 0.010 |
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; both teacher heads agree on what is shown here.
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".