Activation of hedgehog signaling during fracture repair enhances osteoblastic‐dependent matrix formation
Bibliographic record
Abstract
Fracture repair is a well orchestrated process involving various cell types and signaling molecules. The hedgehog signaling pathway is activated in chondrocytes during fracture repair and is known to regulate chondrogenesis however, its role in osteoblasts during injury is yet unknown. In this study we observed tibial fracture repair in mice in which hedgehog signaling was modulated through genetic alterations of the pathway activator, smoothened. Levels of the hedgehog target genes Gli1 and Ptch1 in wildtype mice were upregulated in fracture calluses throughout the repair process. Forced activation of the hedgehog pathway in ubiquitous fashion resulted in increased matrix deposition in the fracture callus. Interestingly, inhibition in chondrocytes did not alter the fracture repair phenotype, while activation of hedgehog in osteoblasts was a requirement for normal fracture repair. In vitro, transcript levels of Gli1 and Ptch1 were elevated during osteoblastogenesis. Activation of hedgehog signaling positively affected osteoblastic differentiation and mineralization as detected using alkaline phosphatase and Von Kossa staining and Alp and Col1 expression. Here we show that the hedgehog signaling pathway plays a critical role in osteoblasts during fracture repair: inhibition of the pathway in osteoblasts leads to decreased matrix at the fracture site while activation increased matrix deposition.
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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 | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 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) | 0.000 | 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".