Increased Osteoblast <scp> Gα <sub>S</sub> </scp> Promotes Ossification by Suppressing Cartilage and Enhancing Callus Mineralization During Fracture Repair in Mice
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Bibliographic record
Abstract
ABSTRACT Gα S , the stimulatory G protein α‐subunit that raises intracellular cAMP levels by activating adenylyl cyclase, plays a vital role in bone development, maintenance, and remodeling. Previously, using transgenic mice overexpressing Gα S in osteoblasts (G S ‐Tg), we demonstrated the influence of osteoblast Gα S level on osteogenesis, bone turnover, and skeletal responses to hyperparathyroidism. To further investigate whether alterations in Gα S levels affect endochondral bone repair, a postnatal bone regenerative process that recapitulates embryonic bone development, we performed stabilized tibial osteotomy in male G S ‐Tg mice at 8 weeks of age and examined the progression of fracture healing by micro‐CT, histomorphometry, and gene expression analysis over a 4‐week period. Bone fractures from G S ‐Tg mice exhibited diminished cartilage formation at the time of peak soft callus formation at 1 week post‐fracture followed by significantly enhanced callus mineralization and new bone formation at 2 weeks post‐fracture. The opposing effects on chondrogenesis and osteogenesis were validated by downregulation of chondrogenic markers and upregulation of osteogenic markers. Histomorphometric analysis at times of increased bone formation (2 and 3 weeks post‐fracture) revealed excess fibroblast‐like cells on newly formed woven bone surfaces and elevated osteocyte density in G S ‐Tg fractures. Coincident with enhanced callus mineralization and bone formation, G S ‐Tg mice showed elevated active β‐catenin and Wntless proteins in osteoblasts at 2 weeks post‐fracture, further substantiated by increased mRNA encoding various canonical Wnts and Wnt target genes, suggesting elevated osteoblastic Wnt secretion and Wnt/β‐catenin signaling. The G S ‐Tg bony callus at 4 weeks post‐fracture exhibited greater mineral density and decreased polar moment of inertia, resulting in improved material stiffness. These findings highlight that elevated Gα S levels increase Wnt signaling, conferring an increased osteogenic differentiation potential at the expense of chondrogenic differentiation, resulting in improved mechanical integrity. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.
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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 | 0.000 | 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 | 0.000 |
| 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 it