CCAAT/enhancer binding protein β regulates expression of matrix metalloproteinase-3 in arthritis
Bibliographic record
Abstract
Objectives: To investigate whether CCAAT/enhancer-binding protein β (C/EBPβ) mediates expression of matrix metalloproteinase-3 (MMP-3) and aggrecanases in arthritis.Methods: Localization of C/EBPβ and MMP-3 in synovium and cartilage from rheumatoid arthritis and osteoarthritis patients was determined by immunohistochemistry. Cell lines, SW982, C28/I2 and human fibroblast-like synoviocytes stimulated by IL-1β were subjected to western blotting and quantitative polymerase chain reaction.Over-expression of C/EBPβ by adenovirus was performed in cells and organ culture of normal cartilage.Knockdown of C/EBPβ by small interference RNA was performed in cells.Activity of the human MMP-3 and aggrecanase-2 (ADAMTS-5) promoters was analyzed by a luciferase assay.To determine whether C/EBPβ directly binds to the MMP-3 or ADAMTS-5 promoter, a chromatin immunoprecipitation (ChIP) assay was performed.Results: Immunohistochemistry showed that C/EBPβ and MMP-3 were co-localized in arthritic synovium and cartilage.Western blots revealed increased C/EBPβ expression in cells treated with IL-1β.Expression of MMP-3, MMP-13, and ADAMTS-5 mRNA was significantly increased by the over-expression of C/EBPβ.C/EBPβ stimulated MMP-3 expression and induced matrix degradation in cartilage explants.C/EBPβ knockdown reduced MMP-3 and ADAMTS-5 expression.C/EBPβ stimulated the 2011 bp MMP-3 promoter and the 1768 bp ADAMTS-5 promoter in a dose-dependent manner.Deletion and mutation analysis of the MMP-3 promoter revealed that the C/EBPβ core responsive element was located between -108 bp and -100 bp.A ChIP assay showed that C/EBPβ directly bound to MMP-3 and ADAMTS-5 promoters.Conclusions: These data demonstrate that C/EBPβ is involved in expression of MMP-3 and ADAMTS-5 in arthritic synovium and cartilage.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 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) | 0.002 | 0.001 |
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".