Role of Kv1.6 channel in chondrocytes in osteoarthritis
Bibliographic record
Abstract
Osteoarthritis (OA) is a chronic inflammatory disease characterized by a decrease in cartilage matrix, disorders of joint movement, and severe pain. Previous studies have suggested that an increase in intracellular Ca2+ concentration ([Ca2+]i) in chondrocytes is associated with OA progression. However, the mechanism underlying this increased [Ca2+]i is unknown. In the present study, we aimed to elucidate this mechanism and its roles in OA progression. Primary chondrocytes were isolated from C57BL/6 mice, and treated with interleukin (IL)-1β, a major cytokine secreted into synovial fluid during OA. In IL-1β-treated chondrocytes, resting membrane potential was depolarized, and resting [Ca2+]i was increased due to the downregulation of voltage-gated K+ channel, Kv1.6. This downregulation of Kv1.6 was also detected in chondrocytes from OA model mice and OA patients. IL-1β induced depolarization of mitochondrial membrane potential (ΔΨm) and cell death. In contrast, overexpression of Kv1.6 in chondrocytes using adenovirus reduced resting [Ca2+]i, increased ΔΨm, and inhibited cell death. In summary, IL-1β downregulates Kv1.6 and increases resting [Ca2+]i, resulting in mitochondrial Ca2+ overload and subsequent cell death. Our findings may contribute to the understanding of OA pathogenesis and the development of new treatments for OA.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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) | 0.001 | 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) | 0.000 | 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".