Activation of ROS/MAPKs/NF-κB/NLRP3 and inhibition of efferocytosis in osteoclast-mediated diabetic osteoporosis.

ABSTRACT: Diabetes mellitus (DM) affects bone metabolism and leads to osteoporosis; however, its pathogenetic mechanisms remain unknown. We found that high glucose (HG) conditions induced the production of reactive oxygen species (ROS) and the expression of proteins related to MAPKs [phosphorylated (p)-ERK, p-JNK, and p-p38], NF-κB (NF-κB, p-IκB, and IKK), and NACHT-LRR-PYD domains-containing protein 3 (NALP3) (NLRP3) [apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC), caspase-1, IL-18, IL-1β, and NLRP3] in osteoclasts (OCs) in vitro. Further analysis showed that in HG-induced OCs, ROS is an upstream signal for MAPKs, NF-κB, and the NLRP3 inflammasome. Moreover, MAPKs mediated the activation of NF-κB and NLRP3, whereas NF-κB up-regulated the

SUBMITTER: An Y 

PROVIDER: S-EPMC6902677 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature