CCL2 But Not CCR2 Is Required for Spontaneous Articular Cartilage Regeneration Post‐Injury
Bibliographic record
Abstract
ABSTRACT The role of the inflammatory response in articular cartilage degeneration and/or repair is often debated. Chemokine networks play a critical role in directing the recruitment of immune cells to sites of injury and have been shown to regulate cell behavior. In this study, we investigated the role of the CCL2/CCR2 signaling axis in cartilage regeneration and degeneration. CCL2 −/− , CCR2 −/− , CCL2 −/− CCR2 −/− , and control (C57) mice were subjected to full‐thickness cartilage defect (FTCD) injuries ( n = 9/group) within the femoral groove. Cartilage regeneration at 4 and 12 weeks post‐FTCD was assessed using a 14‐point histological scoring scale. Mesenchymal stem cells (MSCs) (Sca‐1 + , CD140a + ), macrophages (M1:CD38 + , M2:CD206 + , and M0:F4/80 + ) and proliferating cells (Ki67 + ) were quantified within joints using immunofluorescence. The multi‐lineage differentiation capacity of Sca1 + MSCs was determined for all mouse strains. ACL transection (ACL‐x) was employed to determine if CCL2 −/− CCR2 −/− mice were protected against osteoarthritis (OA) ( n = 6/group). Absence of CCR2, but not CCL2 nor both (CCL2 and CCR2), enhanced spontaneous articular cartilage regeneration by 4 weeks post‐FTCD. Furthermore, increased chondrogenesis was observed in MSCs derived from CCR2 −/− mice. CCL2 deficiency promoted MSC homing to the adjacent synovium and FTCD at both 4 and 12 weeks post‐injury; with no MSCs present at the surface of the FTCD in the remaining strains. Lower OA scores were observed in CCL2 −/− CCR2 −/− mice at 12 weeks post‐ACL‐x compared with C57 mice. Our findings demonstrate an inhibitory role for CCR2 in cartilage regeneration after injury, while CCL2 is required for regeneration, acting through a CCR2 independent mechanism. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2561–2574, 2019
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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 | 0.002 | 0.001 |
| 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".