Role of Lipocalin‐Type Prostaglandin D Synthase in Experimental Osteoarthritis
Bibliographic record
Abstract
Objective Lipocalin‐type prostaglandin D synthase (L‐ PGDS ) catalyzes the formation of prostaglandin D 2 ( PGD 2 ), which has important roles in inflammation and cartilage metabolism. We undertook this study to investigate the role of L‐ PGDS in the pathogenesis of osteoarthritis ( OA ) using an experimental mouse model. Methods Experimental OA was induced in wild‐type ( WT ) and L‐ PGDS –deficient (L‐ PGDS −/− ) mice (n = 10 per genotype) by destabilization of the medial meniscus ( DMM ). Cartilage degradation was evaluated by histology. The expression of matrix metalloproteinase 13 ( MMP ‐13) and ADAMTS ‐5 was assessed by immunohistochemistry. Bone changes were determined by micro–computed tomography. Cartilage explants from L‐ PGDS −/− and WT mice (n = 6 per genotype) were treated with interleukin‐1α ( IL ‐1α) ex vivo in order to evaluate proteoglycan degradation. Moreover, the effect of intraarticular injection of a recombinant adeno‐associated virus type 2/5 (r AAV 2/5) encoding L‐ PGDS on OA progression was evaluated in WT mice (n = 9 per group). Results Compared to WT mice, L‐ PGDS −/− mice had exacerbated cartilage degradation and enhanced expression of MMP ‐13 and ADAMTS ‐5 ( P < 0.05). Furthermore, L‐ PGDS −/− mice displayed increased synovitis and subchondral bone changes ( P < 0.05). Cartilage explants from L‐ PGDS −/− mice showed enhanced proteoglycan degradation following treatment with IL ‐1α ( P < 0.05). Intraarticular injection of r AAV 2/5 encoding L‐ PGDS attenuated the severity of DMM ‐induced OA ‐like changes in WT mice ( P < 0.05). The L‐ PGDS level was increased in OA tissues of WT mice ( P < 0.05). Conclusion Collectively, these findings suggest a protective role of L‐ PGDS in OA , and therefore enhancing levels of L‐ PGDS may constitute a promising therapeutic strategy.
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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 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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) | 0.001 | 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".