Effect of pamidronate on the stimulation of macrophage TNF‐α release by ultra‐high‐molecular‐weight polyethylene particles: a role for apoptosis
Notice bibliographique
Résumé
The demonstration that one of the mechanisms of action of bisphosphonates (BPs) is the induction of osteoclast and macrophage apoptosis, suggests a potent therapeutic role for the BPs and other apoptosis-modulating agents in the management of periprosthetic osteolysis. The purpose of this study was to improve our understanding of the basic underlying molecular events leading to the inhibitory effect of pamidronate on the macrophage response to ultra-high-molecular-weight polyethylene (UHMWPE) particles. Murine J774 macrophages were incubated for 0-72 h in the presence of UHMWPE particles and/or pamidronate. TNF-alpha release was measured by ELISA while poly(ADP-ribose)polymerase (PARP) expression was measured by Western blot. DNA was analyzed on agarose. The appearance of PARP fragment and the fragmentation of DNA were used as markers of apoptosis. We observed a dose-dependent response to UHMWPE particles with TNF-alpha release reaching 4, 10, and 19 times control with 10, 25, and 125 particles/macrophage, respectively. UHMWPE particles (25 particles/macrophage) stimulate TNF-alpha release by a factor of 10, 7, and 6 after 24, 48, and 72 h, respectively, indicating a rapid stimulating effect of UHMWPE particles on TNF-alpha release. Our results also showed that at 10 particles/macrophage, pamidronate inhibits UHMWPE-induced TNF-alpha release by 12%, 14%, and 23% respectively after 24, 48, and 72 h (p<0.05 vs. 24 and 48 h). With 25 particles/macrophage, the inhibition of TNF-alpha reached 9%, 12%, and 15% after 24, 48, and 72 h (p<0.05 vs. 24 h), respectively. There is no significant difference between the inhibition by pamidronate of TNF-alpha release induced by 125 particles/macrophages at 24, 48, and 72 h. When cells are pre-incubated for 48 h with pamidronate prior to addition of UHMWPE particles for 24 h, we observed an increased inhibition of TNF-alpha compared to the co-incubation protocol. The inhibiting effect of pamidronate reaches 56% when pre-incubated with macrophages prior to incubation with 10 particles of UHMWPE/macrophage (p<0.05 vs. co-incubation).Co-incubation of pamidronate with UHMWPE particles also led to the appearance of the proteolytic PARP fragment after 24 h incubation. We also demonstrated the stimulation of DNA fragmentation (DNA laddering) after 48-72 h with pamidronate. The proteolytic cleavage of PARP, an early event in the induction of apoptosis, precedes the inhibition of UHMWPE particle-induced TNF-alpha release by pamidronate whereas the fragmentation of DNA, a late apoptotic event, parallels this inhibition. Our results suggest the induction of macrophage apoptosis is associated with the inhibitory effect of pamidronate on TNF-alpha release. There is a need for the development of medical management of periprosthetic osteolysis. The demonstration that drugs such as pamidronate induce specific apoptosis-related pathways in macrophages contributes data for a rational approach in the treatment and/or prevention of periprosthetic osteolysis.
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 | 0,004 | 0,002 |
| 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 | 0,001 |
| 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 ».