New strategies for the in vivo regulation of metalloprotease gene expression in osteoarthritis chondrocytes by inflammatory mediators
Bibliographic record
Abstract
To study the effect of oral treatment with PD200347, a gabapentinoid (GBP), on osteoarthritis (OA) progression and OA mediators, matrix metalloproteases (MMPs) and the inducible form of nitric oxide synthase (iNOS) expression in a dog experimental model of OA. OA was surgically induced in dogs by sectioning the anterior cruciate ligament. OA dogs were divided into three groups after surgery: group 1, placebo-treated (OA); group 2, oral treatment with 15 mg/kg/day GBP; and group 3, oral treatment with 90 mg/kg/day GBP. Dogs were killed 8 weeks after surgery. The severity of lesions was scored macroscopically and histologically. Cartilage specimens from femoral condyles and tibial plateaus were processed for RNA extraction and quantitative RT-PCR or immunohistochemistry. Specific probes and specific antibodies were used to study IL-1β, iNOS, MMP-1, MMP-3 and MMP-13 mRNA and protein levels, respectively. GBP treatment at both dosages tested (15 or 90 mg/kg/day) dose-dependently reduced the development of cartilage lesions. Quantitative RT-PCR and immunohistochemical analysis showed that GBP treatment also significantly reduced key OA mediator (IL-1β, iNOS, MMP-1, MMP-3 and MMP-13) gene expression and synthesis. This study demonstrated for the first time the effectiveness of a GBP on the reduction of the development of structural changes in the dog OA model. The effect of GBP is mediated through the inhibition, at the transcriptional level, of major mediators of pathophysiological pathways.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| 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) | 0.000 | 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 teacher head, 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".