Role of lamin A/C in the cellular features of age-related bone loss
Bibliographic record
Abstract
Lamin A/C, an important component of the nuclear envelope, has been associated with cell differentiation and tissue development. In bone, recent studies have described that altered function of lamin A/C, due to mutations or incorrect processing, is associated with accelerated and severe bone loss. This could be due to alterations in the differentiation of mesenchymal stem cells (MSC) induced by lack of lamin A/C activity. Therefore, considering that decreased osteoblastogenesis and increased adipogenesis are the characteristic changes observed within bone marrow microenvironment that leads to age-related bone loss, we have studied the effect of inhibition of lamin A/C on MSC into either osteoblasts or adipocytes both in vitro and in vivo. For in vitro studies, we identified the effect of pharmacological inhibition of lamin A/C on adipogenesis. Subsequently, we inhibited lamin A/C by using different doses of lamin A/C siRNA in osteogenic and adipogenic differentiating MSCs as well as normal human osteoblasts. To further verify our results, we have used Zmpste24-/- null progeroid mice that lacks mature lamin A/C and studied the bone changes in absence of mature lamin A/C in in vivo. We have found that partial inhibition of lamin A/C decreased osteoblast differention and function without affecting their survival. Furthermore, our animal studies showed that absence of mature lamin A/C induced a reduction in bone mass and bone quality associated with low bone turnover. In contrast, accumulation of prelamin A induced significant levels of adipogenesis within the bone marrow cavity. In summary, our results provide evidence in support of a pivotal role of lamin A/C in the comm
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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 | 0.001 | 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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 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".