Identification of two populations of osteoarthritic osteoblasts according to the 1,25[OH] <sub>2</sub> vitamin D <sub>3</sub> potency to stimulate osteocalcin
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Bibliographic record
Abstract
INTRODUCTION: Few studies have tried to discriminate a differential behavior between osteoarthritic (OA) osteoblasts (Obs). Based on osteocalcin level, we aimed, in the present study, to evaluate the capacity of OA Obs for producing molecules of the Wnt/β-catenin signaling pathway. METHODS: Human primary OA Obs (n=11) were exposed or not to 50 nM of 1,25 dihydroxyvitamin D3 (VitD3) for 24 h. Osteocalcin (OCN), TGF-β1, Dickkopf-related protein 2 (DKK2), R-spondin 2 (Rspo2), Wnt5b, and low density lipoprotein related-receptor 1 (LRP1) were evaluated by real time RT-PCR. RESULTS: All samples responded to VitD3 as validated by the increase in OCN expression. However two populations of Obs were discriminated; one called "high responders" whose OCN stimulation was higher than 100 fold (mean 881 fold, p<0.01, n=5) and the second one whose stimulation was inferior to 100 fold (mean 47 fold, p<0.01, n=6), namely "low responders". In fact, high responders have a weaker basal expression of OCN. With regards to these two cell populations and in absence of VitD3 challenge, the expression level of TGF-β1 (15 fold, p<0.001), DKK2 (2.5 fold, p<0.002) and Wnt5b (5.5 fold, p<0.003) was higher in "high responders", meanwhile Rspo2 and LRP1 expression was unchanged. VitD3 exacerbated this pattern but corrected OCN expression and favored Wnt agonist expression. CONCLUSION: We identified 2 populations of OA Obs according to the OCN expression under the control of VitD3. In addition under basal conditions, these 2 populations expressed differently TGF-β1, Wnt5b, DKK2, suggesting a heterogeneous differentiation and phenotype in Obs among OA patients.
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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 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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 it