1357 - Short Link N Acts as a Disease Modifying Osteoarthritis Drug
Bibliographic record
Abstract
INTRODUCTION: Osteoarthritis (OA) is a degenerative joint disease characterized by a slowly progressive degradation of articular cartilage, Increased density or erosion of the subchondral bone, formation of osteophytes, inflammation of the synovium, degeneration of ligaments and the menisci, and hypertrophy of the joint capsule. Currently, there is no medical treatment to reverse or even retard OA. The purpose of the present study was to determine if Short Link N (sLN), a recently discovered fragment of the Link N peptide, could retard disease progression in a rabbit model of OA.METHODS: All experiments were conducted with the approval of the Institutional Animal Care and Use Committee. Skeletally mature New Zealand white rabbits underwent unilateral anterior cruciate ligament transection (ACLT) of their left femorotibial joints to induce joint degeneration 1. Beginning 3 weeks post-operatively, and every three weeks thereafter for 12 weeks, either saline (1 mL) or sLN (100 u00b5g in 1 mL saline) was injected intraarticularly in the operated knee. Additional rabbits underwent Sham surgery but without ACLT. The effects on gross morphology and histologic changes were evaluated 2.RESULTS SECTION: In all joint compartments of the Sham group, the articular cartilage had normal macroscopic appearance with no sign of lesion. In the Saline group, fibrillation of articular cartilage occurred in all joint surfaces, and prominent erosion occurred in both femoral condyle compartments and the lateral compartment of the tibial plateau. sLN treatment reduced the severity of the cartilage damage in the 3 compartments of the knee showing erosion. In the lateral tibial plateau and medial femoral condyle sLN prevents the erosion and reduces erosion in the lateral femoral condyle compartment. In the medial tibial plateau compartment, only minor fibrillation is observed with saline or sLN. Overall there is a trend in reducing the severity of joint damage, reaching statistical significance in the MFC compartment. Furthermore, when all histologic parameters were combined from each site to obtain a total joint score, statistically significant differences were detected between the Saline treated joints and the sLN group (Fig 1, p=0.04).DISCUSSION: Overall sLN reduces the severity of joint damage and joint lesion severity in a statistically significant manner. Thus, pharmacologically, sLink N supplementation could be a novel therapeutic approach for treating OA by retarding disease progression.SIGNIFICANCE/CLINICAL RELEVANCE: sLN represents one example that can be useful as a therapeutic agent with the features of a disease modifying osteoarthritis drug.REFERENCES: 1G Tiraloche, C Girard, L Chouinard, J Sampalis, L Moquin, M. Ionescu, AR Poole, Laverty S. Effect of Oral Glucosamine on cartilage degradation in a rabbit model of osteoarthritis. Arthritis and Rheumatism (2005); 52:1118-1128. 2Laverty S, Girard C, Williams JM, Hunziker EB, Pritzker K, The OARSI Histopathology Initiative - Recommendations for Histological Assessments of Osteoarthritis in the Rabbit. Osteoarthritis and Cartilage 18 (2010) S53-S65.ACKNOWLEDGEMENTS: The authors would like to thank our funding sources Canadian Institute of Health Sciences (CIHR) and Trepso Therapeutics.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| 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 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.005 | 0.001 |
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 source (direct Gemma or distilled Codex), 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".