Galectin-3 in osteoarthritis: from a protective to a destructive role
Notice bibliographique
Résumé
Osteoarthritic (OA) chondrocytes are able to re-express numerous genes normally activated in the growth plate, and more particularly in the hypertrophic zone. Among several genes, we are interested in studying galectin-3 (gal-3) since we have recently demonstrated that its expression was increased in OA cartilage [ 1 ]. gal-3 is a mammalian lectin, which interacts with β-galactoside residues and is involved in numerous functions such as adhesion, splicing activity, cell cycle regulation, as well as a receptor for advanced glycation end products (AGE receptor). These functions are related to the gal-3 cellular localization. Indeed, this protein may be found in the plasma membrane, in cytoplasm and in the nucleus. In the present study, we investigated the role(s) of gal-3 using both the monoiodoacetate-induced OA model and in vitro experiments. OA was induced by a single injection of iodoacetate (5 mg/ml, 2 μl) into each knee joint of 4-month-old mice (WT) or gal-3 null mice (KO). Mice were sacrified 7, 14 and 21 days after the single injection. Histologic evaluation was performed on sagittal sections of mouse knee joint. The severity of the OA lesions was graded on a scale of 0–14 in a blinded fashion, by two independent observers, using the histologic/histochemical scale of Mankin. Intracellular and extracellular roles of gal-3 were investigated in both human chondrocytes and in chondrogenic ATDC5 cells, a mouse cell line derived from the 129 strain. Intra-articular injection of monoiodoacetate, which induced osteoarthritis, upregulated the expression of gal-3 in WT mice 7 days post injection, reaching a statistical significance 14 days post injection ( P < 0.05). The histologic grading score indicated that KO mice (control group) had a poorer quality of cartilage compared with WT mice (control group). Moreover, the induction of OA in KO mice showed a marked decreased of bone area, noticeable 7 days post injection ( P < 0.05). According to the results obtained, it seemed that gal-3 was important for the cartilage homeostasis. Colnot and colleagues have suggested that gal-3 could be implicated in chondrocyte survival [ 2 ]. Therefore, we treated OA chondrocytes with sodium nitroprusside (SNP), which is known to generate chondrocyte cell death. Our results showed that gal-3 was much further decreased than was Bcl2 in experiments performed under the same conditions [ 3 ]. Moreover, SNP decreased the gal-3 phosphorylation, which is a key process in the capacity of gal-3 to prevent cell death. Finally, ATDC5 cells transfected with a gal-3-expressing vector were more resistant to SNP-induced cell death compared with those transfected with the empty vector. On the other hand, Ohshima and colleagues found gal-3 in synovial fluid, particularly during inflammation [ 4 ]. Therefore, we investigated the potential role of exogenous gal-3 in chondrocyte cultures. Surprisingly, we found that exogenous gal-3 induced chondrocyte death. One of the most fascinating phenomena is the regulation of gal-3 secretion. Indeed, several cells produced gal-3 but not all are able to secrete a great amount of it, chondrocytes belonging to the latter category. Conversely, gal-3 is secreted in a much greater quantity by inflammatory cells that could affect – at least locally (i.e. at the pannus level) – chondrocyte survival.
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 | 0,000 |
| 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 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,002 |
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 ».