Replication Data for: NLRP3 inflammasome-dependent and -independent interleukin-1β release by macrophages exposed to wear and corrosion products from CoCrMo implants
Bibliographic record
Abstract
Wear particles and metal ions released from cobalt–chromium–molybdenum (CoCrMo) alloy implants present a significant clinical concern. Particles such as Cr2O3 and CoCrMo and metal ions, including Co2+ and Cr3+, have the potential to induce adverse local tissue reactions (ALTR) that can lead to implant failure. The pro-inflammatory response of macrophages to CoCrMo particles, Co2+, or Cr3+ has been shown to involve interleukin-1β (IL 1β) and its putative processing by the NLRP3 inflammasome. The objectives of the present study were to determine: whether IL 1β release by macrophages exposed to Cr2O3 particles (60 nm), CoCrMo particles (3.4 µm), Co2+, or Cr3+ is dependent on NLRP3 and/or caspase 1; whether NLRP3-dependent release is mediated by ROS and/or cathepsin B; and whether caspase-8 is involved when the release is independent of NLRP3. Bone marrow-derived macrophages (BMDM) from wild-type (wt), NLRP3-deficient (Nlrp3-/-), and caspase-1-deficient (Casp1-/-) mice were exposed to the particles or metal ions following priming with lipopolysaccharide. Results showed that IL 1β release by BMDM exposed to the Cr2O3 particles or Cr3+ was NLRP3 dependent. In contrast, IL 1β release induced by the CoCrMo particles or Co2+ was NLRP3 independent being either caspase 1 independent in the case of CoCrMo particles or partly caspase 1 dependent for Co2+. Furthermore, results suggested that NLRP3 inflammasome activation by the Cr2O3 particles was cathepsin B dependent and lysosomal destabilization-mediated, whereas activation by Cr3+ was ROS-mediated. Finally, results suggested that IL 1β release induced by CoCrMo particles or Co2+ was caspase 8 dependent. Overall, these results underscore the specificity and diversity of the mechanisms by which different CoCrMo implant wear particles and metal ions can induce IL-1β release in macrophages. These findings further suggest that targeting NLRP3, caspase 1, and caspase 8 may help reduce the IL 1β–mediated contribution to the inflammatory response induced by periprosthetic wear particles and metal ions from CoCrMo implants. The data set contains all the processed numerical data used to generate the figures presented in the associated article, as well as the full set of raw micrographs.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.006 | 0.015 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.002 |
| Bibliometrics | 0.004 | 0.006 |
| Science and technology studies | 0.005 | 0.002 |
| Scholarly communication | 0.004 | 0.003 |
| Open science | 0.003 | 0.003 |
| Research integrity | 0.004 | 0.003 |
| Insufficient payload (model declined to judge) | 0.447 | 0.179 |
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 source (direct Gemma or distilled Codex), 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".