Testing the efficacy of a human full-length OPG-Fc analog in a severe model of cardiotoxin-induced skeletal muscle injury and repair
Notice bibliographique
Résumé
Although receptor-activator of nuclear factor κB (RANK), its ligand RANKL, and osteoprotegerin (OPG), which are members of the tumor necrosis factor (TNF) superfamily, were first discovered in bone cells, they are also expressed in other cells, including skeletal muscle. We previously showed that the RANK/RANKL/OPG pathway is involved in the physiopathology of Duchenne muscular dystrophy and that a mouse full-length OPG-Fc (mFL-OPG-Fc) treatment is superior to muscle-specific RANK deletion in protecting dystrophic muscles. Although mFL-OPG-Fc has a beneficial effect in the context of muscular dystrophy, the function of human FL-OPG-Fc (hFL-OPG-Fc) during muscle repair is not yet known. In the present study, we investigated the impacts of an hFL-OPG-Fc treatment following the intramuscular injection of cardiotoxin (CTX). We show that a 7-day hFL-OPG-Fc treatment improved force production of soleus muscle. hFL-OPG-Fc also improved soleus muscle integrity and regeneration by increasing satellite cell density and fiber cross-sectional area, attenuating neutrophil inflammatory cell infiltration at 3 and 7 days post-CTX injury, increasing the anti-inflammatory M2 macrophages 7 days post-CTX injury. hFL-OPG-Fc treatment also favored M2 over M1 macrophage phenotypic polarization in vitro. We show for the first time that hFL-OPG-Fc improved myotube maturation and fusion in vitro and reduced cytotoxicity and cell apoptosis. These findings demonstrate that hFL-OPG-Fc has therapeutic potential for muscle diseases in which repair and regeneration are impaired. Although receptor-activator of nuclear factor κB (RANK), its ligand RANKL, and osteoprotegerin (OPG), which are members of the tumor necrosis factor (TNF) superfamily, were first discovered in bone cells, they are also expressed in other cells, including skeletal muscle. We previously showed that the RANK/RANKL/OPG pathway is involved in the physiopathology of Duchenne muscular dystrophy and that a mouse full-length OPG-Fc (mFL-OPG-Fc) treatment is superior to muscle-specific RANK deletion in protecting dystrophic muscles. Although mFL-OPG-Fc has a beneficial effect in the context of muscular dystrophy, the function of human FL-OPG-Fc (hFL-OPG-Fc) during muscle repair is not yet known. In the present study, we investigated the impacts of an hFL-OPG-Fc treatment following the intramuscular injection of cardiotoxin (CTX). We show that a 7-day hFL-OPG-Fc treatment improved force production of soleus muscle. hFL-OPG-Fc also improved soleus muscle integrity and regeneration by increasing satellite cell density and fiber cross-sectional area, attenuating neutrophil inflammatory cell infiltration at 3 and 7 days post-CTX injury, increasing the anti-inflammatory M2 macrophages 7 days post-CTX injury. hFL-OPG-Fc treatment also favored M2 over M1 macrophage phenotypic polarization in vitro. We show for the first time that hFL-OPG-Fc improved myotube maturation and fusion in vitro and reduced cytotoxicity and cell apoptosis. These findings demonstrate that hFL-OPG-Fc has therapeutic potential for muscle diseases in which repair and regeneration are impaired.
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) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 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 | 0,000 |
| 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 ».