Depleting transforming growth factor beta receptor 2 signalling in the cartilage of itga1-null mice attenuates spontaneous knee osteoarthritis
Bibliographic record
Abstract
Objectives Integrin α1β1 protects against osteoarthritis (OA) when it is upregulated in the superficial zone of cartilage in the early stages of disease. However, the mechanism behind this protection is unknown. Integrin α1β1 moderates transforming growth factor β receptor II (TGFBR2) signalling, a critical regulator of chondrocyte anabolic activity. To this end, mice lacking integrin α1β1 have increased baseline activation of TGFBR2 signalling and overall fibrosis. The purpose of this study was to evaluate the interplay between integrin α1β1 and TGFBR2 in the development of spontaneous OA. We hypothesized that dampening TGFBR2 signalling in the cartilage of itga1 -null mice would attenuate OA. Methods Behavioural and histological manifestations of spontaneous knee OA were measured at 4, 8, 12 and 16 months in mice with and without a ubiquitous itga1 deletion and with and without a tamoxifen-induced cartilage specific TGFBR2 depletion. Results Knee cartilage degeneration, collateral ligament ossification and pain responses increased with age. Itga1 -null mice with intact TGFBR2 signalling developed earlier and more severe OA compared to controls. In agreement with our hypothesis, depleting TGFBR2 signalling in the cartilage of itga1 -null mice attenuated OA progression. Conclusion Intact TGFBR2 signalling drives early and worse knee OA in itga1 -null mice. This result supports the hypothesis that the increased expression of integrin α1β1 by superficial zone chondrocytes early in OA development dampens TGFBR2 signalling and thus protects against degeneration.
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 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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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".