Protective Effects of Undenatured Type II Collagen (UC‐II <sup>®</sup> brand) in Animal Models of Rheumatoid Arthritis
Bibliographic record
Abstract
Objective Undenatured Type II Collagen (Lonza's UC‐II ® branded ingredient, Lonza) shows an ability to reduce inflammation of rheumatoid arthritis (RA) and osteoarthritis through oral tolerance, but the mechanisms underlying this protective effect remain unclear. Our goal is to understand how changes in the gut microenvironment affect tolerogenic responses upon oral administration of UC‐II ® supplementation. Hypothesis We hypothesize that systemic inflammation during inflammatory arthritis regulate local tolerogenic responses and inflammation. Identification and further intervention of these pathways may be a promising way to improve the therapeutic activity of UC‐II ® ingredient. Methods Murine Collagen‐Induced Arthritis (CIA) was employed as a model of human RA. Mice with CIA were treated with UC‐II ® supplementation or vehicle by oral gavage (0.66 mg/kg and 5.94 mg/kg for 8 weeks, starting 2 weeks before CIA induction). Incidence and clinical scores were monitored throughout the study period. Animals were culled at week 9, when blood, tissues (gut and lymph nodes) and paws were collected. Histopathological scores were carried out, including H&E staining of gut tissue and paws. Additionally, pro‐inflammatory cytokine IL‐17 and IgGs against collagen were evaluated by ELISA. Immune cell populations in mesenteric lymph nodes (MLNs) and draining lymph nodes (DLNs) were evaluated by flow cytometry. Finally, RT‐PCR was carried out to evaluate expression of inflammatory genes. Results Mice treated with 5.94 mg/kg UC‐II ® supplementation showed a reduced disease incidence compared with CIA control mice, although clinical scores were not altered. However, histological analysis of the joints indicated that UC‐II ® administration reduced cartilage and bone damage. Interestingly, UC‐II ® reverted the reduction of villi length observed in the small intestine of CIA control animals. UC‐II ® treatment affected local and systemic immune responses, since numbers of CD4 T cells, CD8 T cells and B cells in joint draining and mesenteric lymph nodes were significantly modulated. Inflammatory responses were attenuated in UC‐II ® treated mice, evidenced by a reduction in serum antibodies against collagen and a strong reduction in IL‐17 expression. Conclusions UC‐II ® supplementation protected against cartilage and bone damage during murine experimental arthritis. This could be possibly attributed to reduced expression of IL‐17. Blocking of IL‐17 pathway has been shown to have a positive effect on bone and cartilage damage in inflammatory arthritis. Our data suggest that oral administration of UC‐II ® supplementation could represent a novel approach to target this pathway in chronic inflammation. Further understanding of the molecular mechanisms triggered in the gut tissue during RA may pave the way for optimization of UC‐II ® .
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 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 | 0.001 |
| 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 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".