Extracellular Signal-Regulated Kinase Inhibition Modulates Rat Annulus Fibrosus Cell Response to Interleukin-1
Bibliographic record
Abstract
STUDY DESIGN: Rat annulus fibrosus (AF) cells were activated with interleukin-1 (IL-1) with or without extracellular signal-regulated kinase (ERK) inhibition. Factors associated with the anabolic/catabolic balance of the disc were determined. OBJECTIVE: To clarify the role of ERK pathway in AF cells response to IL-1. SUMMARY OF BACKGROUND DATA: IL-1 plays an important role in intervertebral disc degeneration. ERK is an important inflammatory pathway that plays a crucial role in the expression of inflammatory and catabolic genes induced by IL-1 in chondrocytes. However, the role of the ERK pathway in AF cells response to IL-1 has not been fully investigated. METHODS: Rat AF cells in monolayer culture were exposed to IL-1, with or without ERK inhibition; ribonucleic acid was isolated for real time polymerase chain reaction analysis of gene expression, conditioned media analyzed for nitrite, prostaglandin E-2, and IL-6, Western blot was performed to detect the changes of protein expression. RESULTS: ERK specific inhibitor U0126 significantly inhibited IL-1-induced ERK activation. IL-1-dependent upregulation of iNOS, IL-6, Cox-2, (MMP)-3, and MMP-13 was significantly reduced by ERK inhibition. The decreased gene expression of collagen I, collagen II, collagen IX, and IGF-1 induced by IL-1 was also reversed by U0126. Gene expression of ADAMTS-4, ADAMTS-5, and TGF-b were not affected by IL-1 or ERK inhibition. IL-1 moderately upregulated aggrecan and TIMP-1 expression, ERK inhibition had no significant effect on aggrecan expression but decreased TIMP-1 expression in the presence of IL-1. ERK inhibition reversed the changes of protein expression of MMP-3, MMP-13, TIMP-1, aggrecan and collagen II induced by IL-1. IL-1-induced nitric oxide, prostaglandin E-2, and IL-6 accumulation were also reduced by ERK inhibition. CONCLUSION: These results suggest that IL-1 induces an imbalance between anabolic and catabolic events in AF cells, ERK inhibition could provide some protection against the adverse effects of IL-1. LEVEL OF EVIDENCE: N/A.
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How this classification was reachedexpand
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 | 0.000 | 0.000 |
| 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 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.004 | 0.003 |
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; both teacher heads agree on what is shown here.
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".