Prostaglandin D2 Receptors Control Osteoclastogenesis and the Activity of Human Osteoclasts
Bibliographic record
Abstract
We recently showed that human osteoblasts synthesize prostaglandin D(2) (PGD(2)) and express both DP and CRTH2 receptors. Activation of the DP receptor decreased osteoprotegerin production, whereas activation of the CRTH2 receptor induced osteoblast chemotaxis and decreased RANKL expression. Our objectives in this study were to determine the presence, distribution, and action of these receptors in the functions of human osteoclasts and in osteoclastogenesis. Immunohistochemistry was used to detect the presence of DP and CRTH2 in in vitro-differentiated human osteoclasts in culture and in osteoclasts in situ. The effects of the activation of PGD(2) receptors on the cytoskeleton were determined by fluorescence microscopy. Specific agonists and antagonists allowed the study of the roles of these receptors on bone resorption and osteoclast differentiation. Our results show that in vitro-differentiated human osteoclasts and authentic fetal osteoclasts express both DP and CRTH2 receptors, as shown by immunocytochemistry. Similar results were obtained in osteoclasts from normal, osteoporotic, pagetic, and osteoarthritic adult bone tissues. Stimulation of osteoclasts with PGD(2) induced a robust reorganization of the cytoskeleton with a decrease in the number of cells presenting actin rings and an increase of lamellipodia, effects mediated by the DP and CRTH2 receptors, respectively. PGD(2) showed an inhibitory effect on bone resorption activity acting through the DP receptor. In vitro osteoclastogenesis from peripheral blood mononuclear cells cultured in the presence of RANKL and macrophage-colony stimulating factor was decreased by activation of either DP or CRTH2 receptors. These results suggest that PGD(2) receptors could be useful targets in certain bone diseases because their specific activation/inhibition leads to a decrease in osteoclastogenesis and to inhibition of bone resorption by osteoclasts.
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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 | 0.001 | 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 | 0.001 |
| 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".