In Vivo Effects of Osteoblast-Specific Overexpression of Gα s and Gα q/11 on Bone Formation and Bone Remodeling During Fracture Healing
Bibliographic record
Abstract
Abstract Although the regenerative potential of bone is high, fracture healing is sometimes compromised resulting in fracture non-union. Successful prevention and treatment of non-union rely on accurate prognosis of fracture and treatment assignment but are often impeded by a high degree of heterogeneity in fracture pathogenesis and treatment response. Burgeoning evidence that indicates differential levels of G proteins among healthy populations offers a plausible explanation, since G protein signaling plays regulatory roles in bone development and remodeling. We previously demonstrated the in vivo effects of G protein level variation on bone development by characterizing the skeletal phenotypes of two transgenic mouse lines that overexpress normal Gα s (Gs-Tg) or Gα 11 (G11-Tg) in osteoblast lineage cells under the control of the 3.6-kb Col1a1 promoter. Gs-Tg mice showed high bone mass but diminished bone quality due to increased formation of woven bone and cortical porosity. Conversely, G11-Tg mice displayed a low bone mass phenotype with reduced bone strength primarily due to increased bone resorption. It still remains unclear, however, how variation in G protein signaling in osteoblasts affects the rate and quality of bone repair. To characterize bone healing in Gs-Tg and G11-Tg mice, we induced a stabilized transverse osteotomy in the tibia of wild-type, Gs-Tg or G11-Tg at 8 weeks of age and assessed the progression of bone healing at the tissue and molecular levels by Micro-CT, histomorphometry, and quantitative gene expression analysis at 1, 2, 3, and 4 weeks post-fracture. The effects of increased G protein signaling during repair on Wnt and Hh signaling, the two signaling pathways essential in osteogenesis, were also examined by assessing mRNA levels of key components of each pathway. Persistent upregulation of Wnt and Hh signaling in Gs-Tg fractures led to enhanced callus mineralization and new woven bone formation at the expense of cartilaginous callus formation and defective bone remodeling. G11-Tg fractures, in contrast, showed minimal changes in Wnt and Hh pathways and consequently led to only subtle changes in the healing response with a transient increase in callus mineralization followed by its rapid resorption. Our results indicate that G protein signaling in osteoblasts regulates bone formation and remodeling during fracture repair in part by tightly controlling the strength and duration of Wnt and Hh signaling pathways.
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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) | 0.000 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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 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".