Fluorescent mapping of osteocyte-driven bone formation at pre-osteocyte and mature osteocyte lacunae
Bibliographic record
Abstract
Bone modeling and remodeling by osteoblasts and osteoclasts has been considered the primary mechanism of bone metabolism; however, osteocyte bone cells resorb their surrounding perilacunar bone matrix. It is unknown whether perilacunar remodeling contributes to bone formation in the absence of disease, disorder, or other external stimuli. Here, fluorescently labeled bone formation was quantified in femoral cortical bone and vertebral trabecular bone of skeletally mature female C57BL/6 mice (a commonly used mouse strain) using confocal microscopy. To explore whether the osteoblasts, pre-osteocytes, and mature osteocytes equally contributed to bone formation, the number density of lacunae with bone formation and bone formation rate were quantified. Bone formation was observed at both pre-osteocyte and mature osteocyte lacunae. In femoral cortical bone, 89 % of lacunae with bone formation were mature osteocyte lacunae, while in vertebral trabecular bone, 32 % of lacunae with bone formation were mature osteocyte lacunae. Bone formation rate at osteocyte lacunae was 1-2 orders of magnitude lower compared to osteoblast bone formation. Even though perilacunar (re)modeling has a smaller contribution to bone formation, it is an important process that shapes the LCN in pre-osteocyte lacunae during the osteoblast-to-osteocyte transition and maintains bone quality in mature osteocyte lacunae. STATEMENT OF SIGNIFICANCE: Osteoclast and osteoblast bone cells have long been considered the cells responsible for bone remodeling. Here, we quantify the contributions of osteoblasts, pre-osteocytes, and mature osteocytes to bone metabolism in a common mouse strain. We find that perilacunar bone formation occurs at pre-osteocytes and mature osteocytes. In trabecular bone, a greater proportion of lacunae with bone formation were pre-osteocytes because trabecular bone has a high bone turnover. In cortical bone, a greater proportion of lacunae with bone formation were mature osteocytes. In the absence of disease or external stimuli, osteoblasts produce an order of magnitude more bone than at the perilacunar regions. However, perilacunar remodeling is still an important process regulating lacuno-canalicular network morphology and bone quality.
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How this classification was reachedexpand
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 | 0.000 | 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 | 0.000 |
| 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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, 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".