Myoblast paracrine factors induce catabolic remodelling in electrically stimulated myotubes
Bibliographic record
Abstract
Skeletal muscle plasticity is strongly influenced by a multitude of cell populations within the muscle niche. Satellite cells, or resident muscle stem cells, play an essential role in skeletal muscle remodelling after injury where they differentiate into myoblasts and directly donate myonuclei to damaged fibres thereby promoting protein synthesis. Satellite cells have also been shown to act in a paracrine fashion to influence the infiltration of immune cells and other cell types into the skeletal muscle environment to advance regeneration. However, in many degenerative muscular conditions, satellite cell activity is impaired. Moreover, their paracrine mediated signalling directly to muscle fibres remains poorly understood, highlighting a promising therapeutic target for addressing satellite cell dysfunction. The purpose of this project was two-fold: (1) develop an in vitro model of myoblast (MBL) intercellular communication following myotube damage and (2) to determine if MBL proximity alone is adequate for improving tissue repair and reducing cellular stress during recovery. C 2 C 12 -derived myotubes were exposed to 1 h of electrical pulse stimulation (EPS). Immediately following EPS, porous cell inserts containing either myoblasts (MBL+) or no cells (MBL–) were introduced to the damaged myotubes. We employed quantitative protein, mRNA, and morphological analyses of myotubes to characterize the phenotypic response to myoblast signalling. EPS produced Z line sarcomeric disorganization and creatine kinase release from the myotubes, which was mitigated in the MBL + groups ( p < 0.05). A significant main effect of MBL exposure was observed in molecular indicators of muscle repair and metabolism; MBL + myotubes had greater hspa1a gene expression, calpain 3 protein and gene expression, BNIP3 and t-ULK protein expression as compared to MBL– myotubes when recovering from EPS ( p < 0.05). Myotube diameter decreased significantly in MBL + myotubes post-EPS ( p < 0.05). Myoblasts participate in intercellular crosstalk directly to damaged myotubes, and this signalling may increase catabolic processes through the upregulation of contraction-mediated protease activity and autophagic protein content. This research is the first to identify an early, non-fusogenic response mechanism of muscle-resident myoblasts to skeletal muscle in response to damaging stimuli.
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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) | 0.000 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".