Chondrocyte primary cilia lengthening and shortening in response to mediators of osteoarthritis; a role for integrin α1β1 and focal adhesions
Why this work is in the frame
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Bibliographic record
Abstract
Objective: Integrin α1β1 protects against osteoarthritis when it is upregulated in the early stages of disease, however, the mechanism behind this is currently unknown. Hypo-osmotic stress, interleukin-1 (IL-1) and transforming growth factor β (TGFβ) influence chondrocyte signaling and are important mediators of osteoarthritis. Evidence for primary cilia as a signaling hub for these factors and the involvement of the F-actin cytoskeleton in this response is growing. The purpose of this study was to investigate the role of integrin α1β1 in the response of primary cilia and the F-actin cytoskeleton to these osteoarthritic mediators. Design: -null chondrocytes in response to hypo-osmotic stress, IL-1, and TGFβ alone or in combination, and with or without focal adhesion kinase inhibitor. Results: We show that integrin α1β1 and focal adhesions are necessary for cilial lengthening and increases in F-actin peaks with hypo-osmotic stress and IL-1, but are not required for cilial shortening with TGFβ. Furthermore, we established that the chondrocyte primary cilium has a resting length of 2.4 μm, a minimum length of 2.1 μm corresponding to the thickness of the pericellular matrix, and a maximum length of 3.0 μm. Conclusions: While integrin α1β1 is not necessary for the formation of chondrocyte primary cilia and cilial shortening in response to TGFβ, it is necessary for the mediation of cilial lengthening and the formation of F-actin peaks in response to hypo-osmotic stress and IL-1.
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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 | 0.001 |
| 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 it