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Mechanisms of Calcium Pyrophosphate Crystal-induced Inflammation
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Edité par CCSD -
International audience. Hydrated calcium pyrophosphate (CPP) crystal deposition occurs in hyaline and fibrocartilage. Monoclinic and triclinic dihydrated phases, m-CPPD and t-CPPD respectively, are the two phases of CPP crystals identified in human joints and synovial fluids. They are associated with different clinical manifestations including asymptomatic, self-resolving acute arthritis, destructive arthropathies and severe osteoarthritis (1). CPP crystal-induced inflammation is driven mainly by interleukin (IL)-1β production (2). IL-1β activation is a two-step process: a first signal stimulates pro-IL-1β synthesis and the second signal IL-1β maturation and secretion that depend on caspase 1 and NLRP3 inflammasome activation. How different CPPD crystal phases stimulate inflammatory responses remains not understood. We assessed, in vitro, the inflammatory properties of four synthetic CPP phases [m-CPPD, t-CPPD, amorphous CPP (a-CPP) and m-CPPT (tetrahydrate) beta] using human monocyte cell line (THP-1) and mouse bone marrow-derived macrophages. CPP crystals displayed different inflammatory potential: m-CPPD crystals were the most phlogistic one whereas a-CPP and m-CPPT phases induced mild inflammation response. CPP crystal-induced IL-1β production was dependent of NLRP3 inflammasome activation which occurred through several mechanisms. CPP crystal-induced potassium efflux preceded ROS induction and mitochondrial disturbance and was independent of P2X7 channel. Better characterization of cytosolic potassium regulation will permit to identify new therapeutic pathways in microcrystal-related inflammation.
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