Scavenger Receptor of Class B Expressed by Osteoblastic Cells Are Implicated in the Uptake of Cholesteryl Ester and Estradiol From LDL and HDL3
Why this work is in the frame
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Bibliographic record
Abstract
UNLABELLED: Lipoproteins transport many vitamins and hormones that have been shown to be necessary for bone formation. However, the metabolism of LDL and HDL3 by bone-forming osteoblastic cells remains unknown. Here we report that osteoblastic cells express scavenger receptors of class B that are implicated in the uptake of cholesterol and estradiol from LDL and HDL3. INTRODUCTION: The bone tissue is continuously remodeled, and its integrity requires a balance between osteoclastic bone resorption and osteoblastic bone formation. Recent studies have reported the importance of triglyceride-rich lipoproteins for the delivery of lipophilic vitamins necessary for normal bone metabolism. However, the ability of osteoblastic cells to process low- and high-density lipoproteins (LDL and HDL3) and the receptors involved remain unknown. MATERIALS AND METHODS: Binding, competition, degradation, and selective uptake assays with LDL and HDL3 radiolabeled in their protein and lipid moieties or with [3H]estradiol were conducted on human osteoblasts (MG-63 cell line and primary cultures of human osteoblasts [hOB cells]) and on mouse osteoblasts (MC3T3-E1 cell line and primary cultures of murine osteoblasts [mOB cells]). The expression of scavenger receptors (SRs) by osteoblastic cells was determined by RT-PCR and Western immunoblotting, and cellular localization was assessed by sucrose gradient fractionation. RESULTS: Osteoblastic cells were able to bind, internalize, and degrade HDL3 and LDL and are capable of selectively taking up cholesteryl esters (CEs) from these lipoproteins. Also, we provide evidence that osteoblastic cells express SR-BI, SR-BII, and CD36 (SR-Bs receptors) and that these receptors are localized in membrane lipid rafts or caveolin-rich membranes. The selective uptake of CE from LDL and HDL3 by osteoblastic cells was strongly inhibited by the known SR-B ligand oxidized LDL, indicating that SR-B receptors are responsible for the selective uptake. Finally, estradiol carried by LDL and HDL3 was selectively transferred to the osteoblastic cells also through SR-B receptors. CONCLUSIONS: Overall, our results suggest a novel mechanism for the routing of cholesterol and estradiol to osteoblasts involving the metabolism of LDL and HDL3 by SR-B receptors.
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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 | 0.003 | 0.001 |
| 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 | 0.001 |
| 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