Evaluation of Cathepsin-K Activation by Endotoxin and the Effect of Specific Protease Inhibitors on Dentin Matrix
Bibliographic record
Abstract
Host-derived proteases have been shown to be associated with degradation of imperfectly impregnated collagen at the dentin-resin interface. Cathepsins (CTs) have been recently detected in human dentin. CTs can be activated in mild acidic environments that may further activate matrix-metalloproteinases (MMPs). Therapeutic strategies to inhibit dentinal protease activity by MMPs and CTs and subsequently prevent matrix degradation have been gaining importance recently. Chlorhexidine (CHX) (Broad-spectrum antiproteolytic) have been mostly studied. The study aims to evaluate specific CT-K inhibitor in dentin collagen degradation with/without endotoxins. This study specifically aims to (1) Develop demineralized dentin model to assess effectiveness of CT inhibitors, (2) Evaluate effect of specific CT-K inhibitor on dentin collagen properties (3) Evaluate effect of specific CT-K inhibitor on dentin collagen treated with endotoxins. To develop study model, dentin disks with 0.5mm thickness prepared from human molars were completely demineralized in 10%H3PO4. Pulverized dentin powder challenged in 1mL lactic acid (LA) (0.1M, pH5.5). Aliquots of dentin powder were then immersed in 1mL of CHX, E-64 or Odanacatib (ODN) (specific CT-K inhibitor). To evaluate endotoxins effect, dentin powder obtained were challenged with 500EU LPS. Degradation of dentin collagen was determined by sub-product release of C- and N-telopeptides in incubation media. Dentin matrix properties were measured by gravimetric change and ultimate tensile strength. Dentin microstructure was analyzed by scanning electron microscopy (SEM) or atomic force microscopy (AFM). This study showed that LA can activate endogenous CT-K in dentin, this model has potential application for further investigations on activity and possible inhibitors of CT-K in dentin. Specific CTs inhibitors (E-64, ODN) significantly inhibited CT-K activity. Therefore, Dentin therapies targeting enzymes (e.g. CT-K) by specific inhibitors may provide superior pharmacokinetics and optimum efficacy due to precise protein binding, consequently limiting collagen degradation directly or indirectly by enzyme-related pathways. CT-K activity increased within an infected demineralized dentin model. Increased CT-K activity was verified not only by release of C-telopeptides, but for the first time by the increase release of N-telopeptides of type I collagen. The findings from this study suggests that specific CT-K inhibitor (ODN) has the potential to be used in restorative dentistry.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 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".