Overexpression Of Mig-6 In Cartilage Induces An Osteoarthritis-like Phenotype In Mice
Bibliographic record
Abstract
Abstract Background: Osteoarthritis (OA) is the most common form of arthritis and characterized by degeneration of articular cartilage. Mitogen-inducible gene 6 (Mig-6) has been identified as a negative regulator of the Epidermal Growth Factor Receptor (EGFR). Cartilage-specific Mig-6 knockout (KO) mice display increased EGFR signaling, an anabolic buildup of articular cartilage and formation of chondro-osseous nodules. Since our understanding of the EGFR/Mig-6 network in cartilage remains incomplete, we characterized mice with cartilage-specific overexpression of Mig-6 in this study. Methods : Utilizing knee joints from cartilage-specific Mig-6 overexpressing ( Mig- 6over/over ) mice (at multiple time points), we evaluated the articular cartilage using histology, immunohistochemical staining and semi-quantitative OARSI scoring at multiple ages. MicroCT analysis was employed to examine skeletal morphometry, body composition, and bone mineral density. Results: Our data show that cartilage-specific Mig-6 overexpression did not cause any major developmental abnormalities in articular cartilage, although Mig-6 over/over mice have slightly shorter long bones compared to the control group. Moreover, there was no significant difference in bone mineral density and body composition in any of the groups. However, our results indicate that Mig-6 over/over male mice show accelerated cartilage degeneration at 12 and 18 months of age. Immunohistochemistry for SOX9 demonstrated that the number of positively stained cells in Mig-6 over/over mice decreased relative to controls. Immunostaining for MMP13 staining is increased in areas of cartilage degeneration in Mig-6 over/over mice. Moreover, staining for phospho-EGFR (Tyr-1173) and lubricin (PRG4) was decreased in the articular cartilage of Mig-6 over/over mice. Conclusion: Overexpression of Mig-6 in articular cartilage causes no major developmental phenotype; however these mice develop earlier OA during aging. These data demonstrate that Mig-6/EGFR pathways is critical for joint homeostasis and might present a promising therapeutic target for OA.
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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 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 0.002 |
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".