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) implants can trigger adverse local tissue reactions (ALTR) that can lead to implant failure. Identifying mechanisms involved in ALTR, particularly those underlying the initial inflammatory response elicited by wear particles (Cr2O3 and CoCrMo) and metal ions (Co2+ and Cr3+) is therefore critical. The macrophage pro-inflammatory response to CoCrMo particles, Co2+, and Cr3+ includes interleukin-1β (IL-1β) release, a process putatively linked to the NLPR3 inflammasome. However, the effects of Cr2O3 particles remain largely unknown. The objectives of this 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 caspase-1, whether NLRP3-dependent release is mediated by reactive oxygen species (ROS) and/or cathepsin B, and whether caspase-8 is involved when the release is NLRP3 independent. 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. IL-1β release induced by Cr2O3 particles and Cr3+ was shown to be both NLRP3 and caspase-1-dependent. In contrast, IL-1β release induced by CoCrMo particles and Co2+ occurred independently of NLRP3, being caspase-1-independent in response to CoCrMo particles and partially caspase-1-dependent in response to Co2+. Further analysis suggested that NLRP3 inflammasome activation by Cr2O3 particles was cathepsin B dependent and mediated by lysosomal destabilization, whereas activation by Cr3+ was ROS-mediated. NLRP3-independent IL-1β release induced by CoCrMo particles or Co2+ was caspase-8 dependent. Collectively, these findings highlight the diversity and specificity of the mechanisms by which different CoCrMo implant wear particles and metal ions can induce IL-1β release in macrophages. Moreover, they suggest that targeting NLRP3, caspase-1, and/or caspase-8 could help mitigate the IL-1β-mediated component of the inflammatory response triggered by wear particles and metal ions from CoCrMo implants.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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 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".