Tumor necrosis factor alpha modulates fibroblast-like synoviocyte expression of lymphangiogenesis-associated vascular endothelial growth factor C
Bibliographic record
Abstract
Protein lysates were prepared from synovial tissue isolated from seven RA and six OA patients undergoing arthroplasty. Fibroblast-like synoviocytes (FLS) were grown out of synovial tissue samples and used at passages 2–5. Western blotting was employed to examine the VEGF-C isoforms. RT-PCR was used to examine VEGF-C receptors. Western blots revealed an increase in the processed forms of VEGF-C in protein lysates prepared from synovial tissue of RA compared with OA patients. FLS produced substantial amounts of VEGF-C, the majority of which was secreted as the partially processed 29-kDa and 31-kDa forms that have been reported to bind to the lymphangiogenesis-associated VEGFR-3. These secreted forms were increased about 1.6-fold ( P = 0.02) in RA FLS compared with OA FLS. The addition of 10 μg/ml tumor necrosis factor alpha (TNF-α) to the culture media increased the secreted VEGF-C forms an average of 1.4-fold in RA lines and 1.9-fold ( P = 0.002) in OA lines. Additionally, mRNA levels for neuropilin-2, a receptor for VEGF-C and class 3 semaphorins that has been shown to be necessary for the formation of small lymphatic capillaries, were increased approximately 20-fold in both OA and RA lines 24 hours after TNF-α addition. This is the first study to demonstrate that TNF-α-driven FLS may modulate synovial inflammation and joint destruction by paracrine and/or autocrine mechanisms involved in lymphangiogenesis.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| 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) | 0.001 | 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 teacher head, 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".