The potential role of adiponectin in driving arthritis
Notice bibliographique
Résumé
Recent data indicate that adipose tissue synthesizes and releases numerous immunocompetent molecules such as tumor necrosis factor (TNF) alpha, C3a and C1-inhibitor. As adipose tissue is also part of rheumatoid joints, we examined whether adiponectin (apM-1), which has structural homologies to complement proteins and members of the TNF family, and its receptors are present in rheumatoid arthritis (RA) and osteoarthritis (OA) synovium. In addition, owing to the ability of adiponectin to exert several immunmodulatory functions, the effect and regulation of adiponectin-dependent synthesis of proinflammatory and antiinflammatory cytokines was examined. Snap-frozen synovial sections of patients with RA, OA and articular adipose tissue were evaluated by adiponectin and adiponectin receptors type 1 and 2-specific primers, by in situ hybridization using adiponectin riboprobes and antibodies against adiponectin in combination with double-labeling for fibroblasts. In addition, fresh synovial fibroblasts derived from RA and OA patients undergoing knee joint endoprothetic surgery were stimulated with adiponectin in concentrations from 0.2 to 100 μg/ml for 15 hours and compared with unstimulated fibroblasts. Supernatants were examined for production of IL-1β, IL-4, IL-6, IL-10, matrix metalloproteinase (MMP)-1 and MMP-3 by commercially available ELISA. In all patients, strong expression of adiponectin mRNA could be detected in synovial lining and to a lesser extent in synovial sublining. Double-labeling with anti-vimentin (fibroblasts) showed that up to 60% of RA fibroblasts expressed the adiponectin gene and adiponectin type 1 and 2 receptors. Stimulation of synovial fibroblasts with adiponectin showed a dose-dependent upregulation of IL-6 and MMP-1, both in RA and OA synovial fibroblasts. Whereas treatment without or with a small concentration of adiponectin (0.2 μg/ml) resulted only in a low production of IL-6, a concentration-dependent increase could be found with the highest amount produced with 100 μg/ml adiponectin. In contrast, synthesis of IL-1β, IL-4, and IL-10 was not altered by adiponectin stimulation. Of interest, both the TNF inhibitors adalimumab and etanercept were able to downregulate adiponectin-dependent IL-6 and MMP-1 synthesis significantly. The results show that adipocytokines such as adiponectin are not only present in arthritic synovium, but also that adiponectin has stimulatory effects both on the production of distinct cytokines (e.g. IL-6) and of matrix-degrading enzymes (e.g. MMP-1) in synovial fibroblasts. Therefore, the data support the hypothesis that adiponectin may alter the expression of local synovial cytokines and thus may not only represent a candidate gene of a complement/TNF-related pathway operative in RA, but also one of the targets of TNF inhibitor therapy.
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 distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,001 |
| 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 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 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 tête enseignante, 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 ».