Evaluation of Discoidin domain receptor 1 (DDR1) in junctional epithelial permeability and wound healing
Bibliographic record
Abstract
Abstract Background Epithelium is the periodontal first line of defense against microbes. Discoidin domain receptor 1 (DDR1) is a collagen receptor expressed in epithelium. Ddr1 knockout ( Ddr1 −/− ) mice develop periodontitis‐like defects, including junctional epithelium (JE) downgrowth, bacterial invasion, and alveolar bone loss. The objective of this study was to investigate epithelial responses in the absence of DDR1. We hypothesized that Ddr1 −/− mice exhibit increased JE permeability and delayed epithelial wound healing. Methods Epithelium was analyzed in Ddr1 −/− and wild‐type ( Ddr1 +/+ ) mice. JE permeability was studied in vivo by applying a fluorescent dye and measuring dye penetration. Immunohistochemistry (IHC) was used to identify the localization of E‐cadherin and collagens IV, VIII, and XVII in oral epithelium. DDR1 expression in wound healing was confirmed by histology. Epithelial wound healing responses were assessed by creating skin and oral wounds and measuring epithelial migration and wound closure. Results No differences in JE permeability were observed between Ddr1 −/− and Ddr1 +/+ mice, although a trend in the means was observed toward decreased dye surface area ( p = 0.07) and intensity ( p = 0.08–0.09) in the periodontium of the former mice. IHC did not reveal differences in the localization of E‐cadherin or collagens IV, VIII, and XVII between genotypes. In human gingiva, DDR1 was expressed at the epithelial front, migrating to cover palatal wounds. Wound healing experiments revealed a higher % wound healing of dorsal skin in Ddr1 −/− than Ddr1 +/+ mice at 5 days post‐wounding (dpw) ( p = 0.01). Conclusions DDR1 does not affect JE permeability but may play a role in effective epithelial cell migration during cutaneous wound healing. Plain language summary Epithelium is the periodontal first line of defense against microbial attacks. Discoidin domain receptor 1 (DDR1) is a collagen receptor expressed at the epithelium. Mice not expressing the receptor ( Ddr1 −/− mice) develop defects consistent with periodontitis, including epithelium downgrowth and bone loss. In this study, we investigated periodontal epithelial permeability by applying a fluorescent dye in the mouth of Ddr1 +/+ and Ddr1 −/− mice. Additionally, we used histological methods to reveal differences in the localization of gingival proteins between Ddr1 +/+ and Ddr1 −/− . Finally, we investigated the role of DDR1 in wound healing in human sections and in a live animal model. No differences in junctional epithelium (JE) permeability were observed between Ddr1 +/+ and Ddr1 −/− mice, as expressed by the comparable presence of dye in the periodontal tissues of both types of mice. There were no differences in the localization of E‐cadherin or collagens IV, VIII, and XVII between Ddr1 +/+ and Ddr1 −/− . In human gingiva, DDR1 was expressed at the epithelial front, migrating to cover palatal wounds. The animal wound healing study revealed higher healing of skin wounds in Ddr1 −/− than Ddr1 +/+ mice at 5 dpw. In conclusion, this study has elucidated a role for DDR1 in epithelial cell migration during skin wound healing.
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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 | 0.001 | 0.001 |
| 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".