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 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 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".