UNIVERSI
TÄ
TS-
BIBLIOTHEK
P
ADERBORN
Anmelden
Menü
Menü
Start
Hilfe
Blog
Weitere Dienste
Neuerwerbungslisten
Fachsystematik Bücher
Erwerbungsvorschlag
Bestellung aus dem Magazin
Fernleihe
Einstellungen
Sprache
Deutsch
Deutsch
Englisch
Farbschema
Hell
Dunkel
Automatisch
Sie befinden Sich nicht im Netzwerk der Universität Paderborn. Der Zugriff auf elektronische Ressourcen ist
gegebenenfalls
nur via VPN oder Shibboleth (DFN-AAI) möglich.
mehr Informationen...
Universitätsbibliothek
Katalog
Suche
Details
Zur Ergebnisliste
Ergebnis 9 von 10
Datensatz exportieren als...
BibTeX
Bisphosphonate Induces Osteonecrosis of the Jaw in Diabetic Mice via NLRP3/Caspase-1-Dependent IL-1[beta] Mechanism
Journal of bone and mineral research, 2015-12, Vol.30 (12), p.2300
Zhang, Qunzhou
Yu, Weihua
Lee, Sumin
Xu, Qilin
Naji, Ali
Le, Anh D
2015
Volltextzugriff (PDF)
Details
Autor(en) / Beteiligte
Zhang, Qunzhou
Yu, Weihua
Lee, Sumin
Xu, Qilin
Naji, Ali
Le, Anh D
Titel
Bisphosphonate Induces Osteonecrosis of the Jaw in Diabetic Mice via NLRP3/Caspase-1-Dependent IL-1[beta] Mechanism
Ist Teil von
Journal of bone and mineral research, 2015-12, Vol.30 (12), p.2300
Ort / Verlag
Baltimore: Wiley Subscription Services, Inc
Erscheinungsjahr
2015
Quelle
Free E-Journal (出版社公開部分のみ)
Beschreibungen/Notizen
Diabetes mellitus is an established risk factor associated with bisphosphonate-related osteonecrosis of the jaw (BRONJ). Sustained activation of Nod-like receptor (NLR) family, pyrin domain-containing protein 3 (NLRP3) inflammasome contributes to the persistent inflammation and impaired cutaneous wound healing in diabetic mice and human. We have recently demonstrated a compelling linkage between M1 macrophages and BRONJ conditions in both murine and human diseases. The aim of this study was to determine whether NLRP3 inflammasome activation is involved in BRONJ development in diabetic mice. We showed an increased incidence of delayed oral wound healing and bone necrosis of extraction sockets in db/db mice compared with those in nondiabetic db/+ controls, which correlated with an elevated expression of NLRP3, caspase-1, and IL-1[beta] in macrophages residing at local wounds. Constitutively, bone marrow-derived macrophages from db/db mice (db/db BMDMs) secrete a relatively higher level of IL-1[beta] than those from db/+ mice (db/+ BMDMs). Upon stimulation by NLRP3 activators, the secretion of IL-1[beta] by db/db BMDMs was 1.77-fold higher than that by db/+ BMDMs (p<0.001). Systemic treatment of mice with zoledronate (Zol), a nitrogen-containing bisphosphonate, resulted in a 1.86- and 1.63-fold increase in NLRP3/caspase-1-dependent IL-1[beta] secretion by db/+ and db/db BMDMs, respectively, compared with BMDMs derived from nontreated mice (p<0.001). Importantly, systemic administration of pharmacological inhibitors of NLRP3 activation improved oral wound healing and suppressed BRONJ formation in db/db mice. Mechanistically, we showed that supplementation with intermediate metabolites of the mevalonate pathway, inhibitors of caspase-1 and NLRP3 activation, an antagonist for P2X7R, or a scavenger of reactive oxygen species (ROS), robustly abolished Zol-enhanced IL-1[beta] release from macrophages in response to NLRP3 activation (p<0.001). Our findings suggest that diabetes-associated chronic inflammatory response may have contributed to impaired socket wound healing and rendered oral wound susceptible to the development of BRONJ via NLRP3 activation in macrophages. © 2015 American Society for Bone and Mineral Research.
Sprache
Englisch
Identifikatoren
ISSN: 0884-0431
eISSN: 1523-4681
DOI: 10.1002/jbmr.2577
Titel-ID: cdi_proquest_journals_1754629919
Format
–
Weiterführende Literatur
Empfehlungen zum selben Thema automatisch vorgeschlagen von
bX