DELETION OF MBTPS1 IN BONE LEADS TO ENHANCEMENT OF MUSCLE MASS AND FUNCTION IN MATURE MICE
Bibliographic record
Abstract
Cis‐Golgi protease Mbtps1, a proprotein convertase, is responsible for activating a small family of transmembrane spanning b‐ZIP transcription factors. We previously demonstrated Mbtps1 is required for mineralization of osteoblastic cultures. To understand its role in skeletal development, we conditionally deleted MBTPS1 using osteocyte restricted DMP1 Cre recombinase. Despite the absence of an early bone phenotype, KO male mice abruptly begin to gain weight at skeletal maturity. At 40 weeks, knockout mice were 7.3g larger (p=0.034) than littermate controls. MicroCT and piximus analysis of bone and fat content cannot account for this difference in mass. Since MBTPS1 was specifically ablated in osteocytes, we initiated systematic muscle physiological studies to test our recently proposed hypothesis of a bone‐muscle crosstalk axis in health and disease. We found that the extensor digitorum longus and soleus muscles were significantly heavier and stronger in cKO mice as compared to controls. We also observed a leftward shift in their force vs. frequency relationships, suggesting that cKO muscles could be more sensitive to calcium. Interestingly, leptin was found to be 2‐fold higher in serum from cKO mice than controls (p=0.018). We postulate that MBTPS1 ablation in osteocytes leads to augmented serum levels of leptin that acts systemically to alter muscle function. Support: NIH‐NIA P01 AG039355 and MOLSRB.
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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 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| 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".