Abstract 36: Menin Functions Critically In Mesenchymal Stem Cells And Osteoblast Progenitors To Promote Bone Development And Maintenance In Vivo
Bibliographic record
Abstract
Purpose: Menin, the MEN1 gene product, is expressed in many tissues, including bone, where its function in-vivo remains poorly understood. Methods: Conditional knockout of the Men1 gene in mice was achieved using the Cre-LoxP recombination system: Prx1-Cre;Men1f/f, Osx-Cre;Men1f/f and OC-Cre;Men1f/f represent the deletion of menin in the mesenchymal stem cell, osteoblast progenitor, and mature osteoblast, respectively. Results: Skeletal phenotyping performed at 6 months demonstrated significantly reduced BMD and femur length in the Prx1-Cre; Men1f/f and Osx-Cre; Men1f/f strains. By 3-dimensional micro-CT imaging, all three strains of knockout mice showed decreased trabecular bone volume, altered trabecular structure, and decreased cortical bone thickness. Femur stiffness and ultimate force were reduced in Prx1-Cre; Men1f/f mice as assessed using 3-point bending tests. Primary calvarial osteoblasts of all strains of knockout mice were deficient in mineralization using Alizarin red staining, and exhibited altered gene expression profiles. Osteoblasts from heterozygous (Osx-Cre; Men1+/f) mice were intermediate in this respect. Serum biochemistries were unaffected. By contrast, whereas OC-Cre; Men1f/f mice exhibited reduced numbers of osteoblasts, increased osteocyte density and decreased osteoclast number, Prx1-Cre; Men1f/f and Osx-Cre; Men1f/f mice had marked increases in osteoclast number and unaltered number of osteoblasts. This is consistent with in vitro and in vivo findings of increased RANKL/OPG mRNA ratios supporting increased osteoclastogenesis. Conclusions: We conclude that osteoblast menin plays a crucial role in bone development and maintenance of bone mass in vivo, and may serve as a potential gain-of-function therapeutic target for bone development and regeneration.
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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 | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.005 | 0.002 |
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".