Advanced glycation endproducts in the development of osteoarthritis
Notice bibliographique
Résumé
Osteoarthritis (OA) is one of the most prevalent and disabling chronic conditions affecting the elderly. The most prominent feature of OA is the progressive destruction of articular cartilage resulting in impaired joint motion, severe pain and, ultimately, disability. Age is identified as the main risk factor for the development of OA, but the mechanism by which aging is involved still remains largely unclear. Age-related changes in the articular cartilage could play an important role in the susceptibility of cartilage to OA. One of the major age-related changes in articular cartilage is the accumulation of advanced glycation endproducts (AGEs), resulting from the spontaneous reaction of reducing sugars with proteins. The present studies were designed to investigate whether AGE accumulation in cartilage may predispose to the development of OA. The role of AGEs in the development of OA was studied by a combination of in vitro , ex vivo and in vivo experiments. The type and quantity of AGEs in human articular cartilage were determined using HPLC and GC-MS methods. Effects of AGE accumulation on cartilage extracellular matrix turnover were assessed in human articular cartilage and bovine alginate cultures using radiolabel incorporation, colorimetric, enzyme activity and HPLC analyses. The in vivo role of AGEs in OA predisposition was studied in the canine ACLT model for OA. High levels of all well-characterized AGEs (pentosidine, carboxymethyllysine and carboxyethyllysine) accumulate with age in cartilage collagen. Furthermore, an age-related increase of general measures of AGEs (fluorescence at 370/440 nm, browning, and amino acid modification) was also observed [ 1 ]. Accumulation of AGEs was correlated with increased stiffness and brittleness of the cartilage, rendering it more prone to mechanical damage. In addition to affecting the mechanical properties of tissues, articular cartilage chondrocytes show decreased proteoglycan and collagen synthesis at increased AGE levels. Degradation of AGE-modified collagen by matrix metalloproteinases is impaired compared with unmodified collagen. In a canine study of experimentally induced OA by anterior cruciate ligament transection, animals with elevated AGE levels suffered from more severe OA than those with normal AGE levels [ 2 ]. Moreover, in a cross-sectional study using human articular cartilage samples obtained at autopsy, the presence of cartilage degeneration was associated with higher AGE levels in the joint cartilage. AGE accumulation in cartilage leads to decreased mechanical properties (increased stiffness and brittleness) and impaired extracellular matrix turnover (decreased synthesis and degradation). Together these data support the hypothesis presented in Fig. 1 that the age-related accumulation of AGEs changes the properties of articular cartilage and thereby renders the tissue more prone to the development of OA. Hypothesis of how advanced glycation endproduct (AGE)-related accumulation of AGEs could predispose to the development of osteoarthritis (OA).
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 | 0,002 | 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 ».