Expression and Function of Histone Deacetylases in Rheumatoid Arthritis Synovial Fibroblasts
Bibliographic record
Abstract
OBJECTIVE: To explore the effects of histone deacetylases (HDAC) on rheumatoid arthritis synovial fibroblasts (RA-SF). METHODS: The expression of mRNA encoding HDAC1 through HDAC11 in RA-SF and osteoarthritis-SF (OA-SF) was determined using real-time polymerase chain reactions. The functions of HDAC1 and HDAC2 in RA-SF were assessed using small interfering RNA (siRNA) technology. Cell counts and proliferation were examined by MTT assays and BrDU ELISA, respectively, and apoptosis was determined using the TUNEL assay and annexin V staining. Levels of cell cycle-related molecules and matrix metalloproteinases (MMP) were tested by Western blotting and ELISA, respectively. RESULTS: Messenger RNA expression of HDAC1 was significantly higher in RA-SF than in OA-SF. Knockdown of HDAC1 and HDAC2 by siRNA resulted in decreased cell counts and cell proliferation, and increased apoptosis in RA-SF. Expression of p16, p21, and p53 was increased by knockdown of both HDAC1 and HDAC2. On the other hand, knockdown of HDAC1, but not of HDAC2, upregulated tumor necrosis factor-alpha-induced MMP-1 production by RA-SF. CONCLUSION: HDAC1 is overexpressed in RA-SF compared to OA-SF. HDAC1 supports cell proliferation and survival of RA-SF, but suppresses MMP-1 production. HDAC2 also plays an important role in cell proliferation and apoptosis of RA-SF. Our study provides useful information to develop new HDAC inhibitors for the treatment of RA.
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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 | 0.001 | 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) | 0.000 | 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".