Production of Prostaglandin D2 by Human Osteoblasts and Modulation of Osteoprotegerin, RANKL, and Cellular Migration by DP and CRTH2 Receptors
Bibliographic record
Abstract
UNLABELLED: Human osteoblasts produce PGD(2), which acts on the DP receptor to decrease osteoprotegerin production and on the CRTH2 receptor to decrease RANKL expression and to induce osteoblast chemotaxis. These results indicate that activation of CRTH2 may lead to an anabolic response in bone. INTRODUCTION: Whereas the actions of prostaglandin (PG)E(2) as a modulator of bone and osteoblast function are relatively well characterized, little is known about PGD(2) and bone metabolism. The objectives of this study were to determine if human osteoblasts can produce PGD(2), which prostaglandin D(2) synthases are implicated in this synthesis, to identify the PGD(2) receptors (DP and CRTH2) on these cells and to characterize the biological effects resulting from their activation. MATERIALS AND METHODS: RT-PCR analysis and immunohistochemistry were used to detect PGD(2) receptor and synthases in cultured human osteoblasts. Immunohistochemistry was used to identify the synthases and receptors in human bone tissue. Intracellular cAMP and calcium levels were determined to verify receptor activation. The cells were stimulated with PGD(2) or the specific agonists BW 245C (DP) and DK-PGD(2) (CRTH2), and the resulting effects on osteoprotegerin (OPG) secretion, RANKL expression, and chemotaxis were determined. Osteoblast production of PGD(2) was evaluated by measuring PGD(2) in the culture supernatants after stimulation with interleukin (IL)-1, TNF-alpha, PTH, vascular endothelial growth factor (VEGF), and insulin-like growth factor I (IGF-I). RESULTS: Human osteoblasts in culture generated PGD(2) when stimulated. Both osteoblasts in culture and in situ present the lipocalin-type PGD(2) synthase only. Both DP and CRTH2 receptors were present in human osteoblasts in culture and in situ. Stimulation of DP resulted in an increase in cAMP, whereas CRTH2 increased the intracellular calcium level. OPG production was reduced by 60% after DP receptor stimulation, whereas CRTH2 receptor stimulation decreased RANKL expression on human osteoblasts. As reported for other cell types, CRTH2 was a potent inducer of chemotaxis for human osteoblasts in culture. CONCLUSIONS: Human osteoblasts in culture produce PGD(2) under biologically relevant stimuli through the lipocalin-type PGD(2) synthase (L-PGDS) pathway. As an autacoid, PGD(2) can act on DP and CRTH2 receptors, both present on these cells. Specific activation of CRTH2 could lead directly and indirectly to an anabolic response in bone.
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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 | 0.000 |
| 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".