ASBMR 25th Annual Meeting 1001–1222
Bibliographic record
Abstract
We previously reported that neonatal mice with targeted disruption of the PTH gene (PTH -/-) have decreased trabecular bone volume in long bones due to decreased osteoblast numbers in the primary spongiosa.At 4 months of age, however, PTH -/-mice have increased trabecular bone volume.Haploinsufficient PTHrP +/-mice are normal at birth but at 4 months have decreased trabecular bone volume.To determine whether PTHrP plays any role in maintaining higher bone mass in postnatal PTH -/-mice, we generated mice which are homozygous for the PTH null allele and heterozygous for the PTHrP null allele (PTH -/-; PTHrP +/-) and compared these to wild type and to PTH -/-mice.At 4 months of age, PTH -/-; PTHrP +/-mice displayed similar biochemical alterations as PTH -/-mice, i.e. they had undetectable PTH levels and were hypocalcemic, hyperphosphatemic, had enlarged parathyroid glands and decreased serum 1,25-dihydroxy vitamin D 3 (1,25(OH) 2 D 3 ) levels.Trabecular bone volumes of tibiae, femora and vertebrae were increased by 148%, 156% and 159%, respectively, in PTH -/-mice compared to their wild littermates, but were decreased in PTH -/-; PTHrP +/-mice by 37%, 36% and 36%, respectively, compared to their wild type littermates, and by 58%, 59% and 60%, respectively, compared to PTH -/-mice.Alkaline phosphatase positive osteoblast numbers and bone formation rates (assessed by double-calcein labeling) were decreased in PTH -/-mice, and even more dramatically decreased in PTH -/-; PTHrP +/-mice compared to their wild type littermates.The number and size of TRAP positive osteoclasts were also diminished in PTH -/-mice, and more prominently reduced in PTH -/-; PTHrP +/-mice compared to their wild type littermates.This reduction was associated with a decrease in RANKL positive osteoblasts as demonstrated by immunohistochemical staining.Bone levels of PTHrP mRNA as determined by RT-PCR and immunohistochemical levels of PTHrP in osteoblasts were enhanced in PTH -/-mice, but not in PTH -/-; PTHrP +/-mice compared to their wild type littermates.These studies show that PTHrP haploinsufficiency can reduce further the decreased bone turnover in PTH deficient animals and that the increased postnatal trabecular bone volume observed in PTH deficient animals is dependent on the action of PTHrP.PTHrP therefore is an important mediator of postnatal bone growth.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.002 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.003 | 0.001 |
| Open science | 0.001 | 0.002 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.512 | 0.554 |
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; the direct Gemma label and the distilled Codex classifier agree on what is shown here.
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".