Endothelial nitric oxide synthase deficiency in mice results in reduced chondrocyte proliferation and endochondral bone growth
Bibliographic record
Abstract
OBJECTIVE: Nitric oxide (NO) and aberrant chondrocyte differentiation have both been implicated in the pathogenesis of osteoarthritis, but whether these processes are connected is unknown, and the role of specific NO synthase (NOS) enzymes in chondrocyte physiology is unclear. This study was undertaken to examine the effects of inactivation of endothelial cell NOS (eNOS) on cartilage development in mice. METHODS: Skeletal growth and development of mice carrying a null mutation in the eNOS gene was compared with that of their control littermates. In situ analyses were complemented by experiments with primary chondrocytes and tibial explants from these mice. RESULTS: Mice that were deficient in eNOS showed increased fatality and reduced bone growth, with hypocellular growth plates and a marked reduction in the number of proliferating chondrocytes. In vitro studies demonstrated lower chondrocyte numbers and reduced endochondral bone growth in mutant mice, suggesting that the role of eNOS signaling in chondrocyte proliferation is cell autonomous. Reduced chondrocyte numbers appear to be caused by decreased cyclin D1 and increased p57 expression in mutant mice, resulting in slower cell cycle progression and earlier cell cycle exit. In addition, expression of early chondrocyte markers such as SOX9 was reduced, and prehypertrophic markers were expressed prematurely in mutant mice. CONCLUSION: Our findings identify a novel and important role of eNOS in chondrocyte proliferation and endochondral bone growth and demonstrate that loss of eNOS results in premature cell cycle exit and prehypertrophic chondrocyte differentiation during cartilage development.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| 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".