Calcium silicate induces mitophagy-mediated metabolic shifts toward oxidative phosphorylation in BMSCs to facilitate osteogenesis and bone regeneration
Why this work is in the frame
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Bibliographic record
Abstract
Calcium silicate (CS)-based bioactive materials were widely utilized to promote the therapeutic potential of bone marrow mesenchymal stem cells (BMSCs) in bone tissue engineering. The activation of numerous classic bone formation modulators, including the BMP, Wnt, and MAPK/ERK signaling pathways, contributes to the CS-induced osteogenesis of BMSCs. Mitochondrial metabolic patterns have emerged as key contributors to the osteogenic differentiation of mesenchymal stem cells. However, whether CS affects the mitochondrial metabolic profiles of BMSCs is mostly unclear. Herein, we showed that CS induced the osteogenic differentiation of human BMSCs (hBMSCs) mainly via silicon (Si) ion release. Moreover, CS-stimulated hBMSCs underwent metabolic reprogramming accompanied by increased mitochondrial oxidative phosphorylation (OXPHOS) activity. The inhibition of OXPHOS hindered the CS-induced osteogenic differentiation of hBMSCs and bone regeneration, indicating that CS-induced OXPHOS mediated the observed increase in osteogenesis. Mechanistically, CS induced mitophagy and autophagic flux by increasing the formation of autolysosomes and lysosomal degradation to eliminate dysfunctional mitochondria and mitochondrial reactive oxygen species production, leading to enhanced OXPHOS and osteogenesis in hBMSCs. Furthermore, CS promoted mitochondrial fusion in hBMSCs, which may contribute to OXPHOS activation. Our investigation reveals a previously unclear function of CS in regulating the osteogenesis of BMSCs by inducing mitophagy-mediated metabolic shifts toward OXPHOS.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| 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 it