Crosstalk between Bone and Muscle: Deletion of Mbtps1 in Bone Leads to Age‐Dependent Increase in Muscle Size and Contractile Function
Bibliographic record
Abstract
Proprotein convertase Mbtps1 is required for transcription of bone matrix proteins including fibronectin, collagen XI, and PHEX by osteoblastic/osteocytic cells. Since complete loss of Mbtps1 is lethal at E4, we asked if conditional deletion of Mbtps1 using early osteocyte DMP1 cre would disrupt bone structure. Mbtps1 cKO male mice were slightly larger than controls (43.6 g vs. 40.2 g, p=0.057) but displayed no significant changes in bone dimensions, BMD, mineral content, or cortical/trabecular bone parameters at 12 and 40 weeks of age. However, 40 week old soleus muscles from cKO mice weighed 20% more and contracted with 50% more force ex vivo even when normalized for size despite the fact that Mptps1 expression was unchanged (0.94 cKO/control +/‐ 0.42 STD). Immunostaining revealed cKO soleus muscles contained about 35% type I and 60% type 2 myosin heavy chain positive cells, were devoid of myosin 2b fiber+ cells which comprised 5% of control cells, and displayed a higher percentage of central nuclei than controls. Central nuclei, which can reflect muscle repair or regeneration, were restricted to type I myosin heavy chain positive cells. The osteocyte specific deletion of Mbtps1 along with genome arrays that demonstrate increased expression of muscle performance markers such as α‐actinin3 support a cross‐talk signaling mechanism by which Mbtps1‐deficient bone cells increase muscle contractile function in adult mice. Revealing the molecular mechanism responsible could lead to new therapies for a host of muscle disorders.
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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 | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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".