Octacalcium phosphate crystals directly stimulate expression of inducible nitric oxide synthase through p38 and JNK mitogen-activated protein kinases in articular chondrocytes

摘要: Basic calcium phosphate (BCP) crystals, including hydroxyapatite, octacalcium (OCP) and carbonate-apatite, have been associated with severe osteoarthritis several degenerative arthropathies. Most studies considered the chondrocyte to be a bystander in pathogenesis of crystal deposition disease, assuming that synovial cell cytokines were only triggers activation. In present study we identified direct activation articular chondrocytes by OCP which are BCP crystals greatest potential for inducing inflammation. induced nitric oxide (NO) production inducible synthase (NOS) mRNA expression isolated cartilage fragments, dose-dependent manner variations over time. also IL-1β expression. Using pharmacological cytokine inhibitors, observed NO NOS regulated at both transcriptional translational levels; independent from gene activation; involved p38 c-Jun amino-terminal kinase (JNK) mitogen-activated protein (MAPK) pathways, as further confirmed crystal-induced JNK MAPK phosphorylation. Taken together, our data suggest response probably under control activator protein-1. NO, major mediator degradation, can directly produced chondrocytes. Together activation, this mechanism may important destructive arthropathies triggered microcrystals.