Protective Effects of Undenatured Type II Collagen (UC‐II <sup>®</sup> brand) in Animal Models of Rheumatoid Arthritis
Notice bibliographique
Résumé
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 ® .
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,001 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».